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One CT scanner and one DR system closest to the emergency department are designated the fever-CT and fever-DR to examine patients with suspected and confirmed COVID-19. There is a separate dedicated access between the contaminated area and the fever screening tents. The semicontaminated area includes the fever-CT control room, fever-DR control room, and other patient examination access areas. The buffer zone includes access areas for medical personnel and a dressing area for technologists. The clean area includes the administrative office and the diagnostic room. The contaminated area was isolated from other areas using physical barricades. Directional signs were newly installed to guide patients and staff. | [
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The design of the surveys was in accordance with WHO recommendations [7] . The design effect factor due to cluster sampling was estimated at 1.28 [8] . A sample size of 52500 adults (≧15 years old), in 35 clusters, was calculated based on detecting a change of 20% in prevalence rate of TB smear positive cases compared with the rate of the 2000 survey (95 per 100,000), with a probability greater than 95% and 95% power, accounting for 90% response rate of participants [9] . A stratified multi stage random sampling was used to select the 35 clusters within 17 prefectures in Shandong province. The number of clusters was randomly allocated in proportion to the provincial population at the prefectural, county/district and township levels. A cluster was defined as a community (a village in the rural area or a resident community in an urban area) with a population of 1250 to 1750 adults (i.e., those of 15 years or older). | [
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casei by cloning, as described previously [26, 27] . The sM2 gene was modified by adding a Kpn I site at the 59 terminal and Sal I at the 39 terminal for cloning. The polymerase chain reaction (PCR) was performed to amplify the gene using the primer pair 59-GGGGTACCTCATTATTAACA-39, and 59-ACGTCGACT-CATTATTCAAGTTCAATAATG AC-39. Similarly, a BamH I site at the 59 terminal and a Kpn I site at the 39 terminal end were added to the CTA1 gene using primers 59-CGGGATCCAAT-GATGATAAGTTATAT-39 and 59-GGGT ACCCGAT-GATCTTGGAGC ATT-39. The modified genes were ligated into the T Easy Vector (Invitrogen, Seoul, Korea). Genes were then digested with Kpn I-Sal I for sM2 and BamH I-Kpn I for CTA1. | [
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observed how the interferon pathway helped keep the infections in check, before creating a computer model of this response. The experiments and model helped reveal that the bats' defenses may have a potential downside for other animals, including humans. In both bat species, the strongest antiviral responses were countered by the virus spreading more quickly from cell to cell. This suggests that bat immune defenses may drive the evolution of faster transmitting viruses, and while bats are well protected from the harmful effects of their own prolific viruses, other creatures like humans are not. The findings may help to explain why bats are often the source for viruses that are deadly in humans. Learning more about bats' antiviral defenses and how they drive virus evolution may help scientists develop better ways to predict, prevent or limit the spread of viruses from bats to humans. | [
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The combined use of the ECoVent device with the RTube™ allowed the registration of the exhaled volume and breathing frequency during collection. In this way, the number of exhaled viral particles per liter air or per minute can theoretically be estimated. RESULTS: Viral screening resulted in the detection of 4 different viruses in EBC and/or nasal swabs: Rhinovirus, Human Respiratory Syncytial Virus B, Influenza A and Influenza B. Rhinovirus was detected in 6 EBCs and 1 EBC was Influenza B positive. We report a viral detection rate of 7% for the EBCs, which is much lower than the detection rate of 46.8% observed using nasal swabs. CONCLUSION: Although very promising, EBC collection using the RTube™ is not reliable for diagnosis of respiratory infections. Text: Human respiratory tract infections represent the most commonly encountered infections worldwide. | [
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It is then noteworthy that one study reported an association between higher loads in the URT and worse clinical outcome including intensive care and death [94] . At writing, no human data exist to define whether the virus replicates solely or preferentially in the LRT or URT, or replicates in other human tissues in vivo although MERS-CoV RNA has been detected from both the URT and LRT in a macaque monkey model [100] .The distribution of DPP4 in the human upper airways is also not well described. Individual human case studies report long periods of viral shedding, sometimes intermittently and not necessarily linked to the presence of disease symptoms. [25, 69, 99, 101] In one instance, a HCW shed viral RNA for 42 days in the absence of disease [99] . It is an area of high priority to better understand whether such cases are able to infect others. Over three quarters of MERS cases shed viral RNA in their LRT specimens (tracheal aspirates and sputum) for at least 30 days, while only 30 % of contacts were still shedding RNA in their URT specimens [91, 102] . | [
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Spain has recently seen a large increase in the number of deaths, and given its smaller population, our model estimates that a higher proportion of the population, 15.0% (7.0 [18-19] million people) have been infected to date. Germany is estimated to have one of the lowest attack rates at 0.7% with 600,000 [240,000-1,500,000] people infected. Imperial College COVID-19 Response Team Table l: Posterior model estimates of percentage of total population infected as of 28th March 2020. Country % of total population infected (mean [95% credible intervall) Austria 1.1% [0.36%-3.1%] Belgium 3.7% [1.3%-9.7%] Denmark 1.1% [0.40%-3.1%] France 3.0% [1.1%-7.4%] Germany 0.72% [0.28%-1.8%] Italy 9.8% [3.2%-26%] Norway 0.41% [0.09%-1.2%] Spain 15% [3.7%-41%] Sweden 3.1% [0.85%-8.4%] Switzerland 3.2% [1.3%-7.6%] United Kingdom 2.7% [1.2%-5.4%] 2.2 Reproduction numbers and impact of interventions Averaged across all countries, we estimate initial reproduction numbers of around 3.87 [3.01-4.66], which is in line with other estimates.1'8 These estimates are informed by our choice of serial interval distribution and the initial growth rate of observed deaths. A shorter assumed serial interval results in lower starting reproduction numbers (Appendix 8.4.2, Appendix 8.4.6). The initial reproduction numbers are also uncertain due to (a) importation being the dominant source of new infections early in the epidemic, rather than local transmission (b) possible under-ascertainment in deaths particularly before testing became widespread. | [
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Irving et al. (2010) describe at least one reason for this lack of success: it seems that peptide antigens elicit a set of topologically restricted antibodies that are largely unable to recognize discontinuous or complex epitopes on larger biomolecules. While the peptide may mimic the chemistry of a given epitope on a folded protein (allowing it to crossreact with a targeted antibody), being a smaller molecule, it cannot mimic the topology of that antibody's full epitope. Despite this, the filamentous phage remains highly useful as a carrier for peptides with relatively simple secondary structures, which may be stablilized via anchoring to the coat proteins (Henry et al., 2011) . This may be especially true of peptides with poor inherent immunogenicity, which may be increased by high-valency display and phage-associated adjuvanticity (see Immunological Mechanisms of Vaccination with Filamentous Phage below). The filamentous phage has been used to a lesser extent as a carrier for T-cell peptide epitopes, primarily as fusion proteins with pVIII ( Table 3) . | [
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The VEE replicon systems are particularly appealing as the VEE targets antigen-presenting cells in the lymphatic tissues, priming rapid and robust immune responses [73] . VEE replicon systems can induce robust mucosal immune responses through intranasal or subcutaneous immunization [72] [73] [74] , and subcutaneous immunization with virus-like replicon particles (VRP) expressing HA-induced antigen-specific systemic IgG and fecal IgA antibodies [74] . VRPs derived from VEE virus have been developed as candidate vaccines for cytomegalovirus (CMV). A phase I clinical trial with the CMV VRP showed the vaccine was immunogenic, inducing CMV-neutralizing antibody responses and potent T cell responses. Moreover, the vaccine was well tolerated and considered safe [75] . A separate clinical trial assessed efficacy of repeated immunization with a VRP expressing a tumor antigen. | [
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The concomitant development of steroid resistance together with recurring or prolong viral infection thus added considerable burden to the management of acute exacerbation, which should be the future focus of research to resolve the dual complications arising from viral infection. On the other end of the spectrum, viruses that induce strong type 1 inflammation and cell death such as IFV (Yan et al., 2016; Guibas et al., 2018) and certain CoV (including the recently emerged COVID-19 virus) (Tao et al., 2013; Yue et al., 2018; Zhu et al., 2020) , may not cause prolonged inflammation due to strong induction of antiviral clearance. These infections, however, cause massive damage and cell death to the epithelial barrier, so much so that areas of the epithelium may be completely absent post infection (Yan et al., 2016; Tan et al., 2019) . Factors such as RANTES and CXCL10, which recruit immune cells to induce apoptosis, are strongly induced from IFV infected epithelium (Ampomah et al., 2018; Tan et al., 2019) . Additionally, necroptotic factors such as RIP3 further compounds the cell deaths in IFV infected epithelium . The massive cell death induced may result in worsening of the acute exacerbation due to the release of their cellular content into the airway, further evoking an inflammatory response in the airway (Guibas et al., 2018) . | [
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Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection. Text: Coronaviruses (CoVs) are enveloped, positive-sense, single-stranded RNA viruses that belong to the subfamily Coronavirinae, family Coronavirdiae, order Nidovirales. There are four genera of CoVs, namely, Alphacoronavirus (αCoV), Betacoronavirus (βCoV), Deltacoronavirus (δCoV), and Gammacoronavirus (γCoV) [1] . Evolutionary analyses have shown that bats and rodents are the gene sources of most αCoVs and βCoVs, while avian species are the gene sources of most δCoVs and γCoVs. CoVs have repeatedly crossed species barriers and some have emerged as important human pathogens. | [
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While these two instances do not suggest Ad-vector vaccines are unsafe or inefficacious, the umbra cast by the clinical trials notes has affected interest for all adenovirus vaccines, but interest still remains. Immunization with adenovirus vectors induces potent cellular and humoral immune responses that are initiated through toll-like receptor-dependent and independent pathways which induce robust pro-inflammatory cytokine responses. Recombinant Ad vaccines expressing HA antigens from pandemic H1N1 (pH1N1), H5 and H7 highly pathogenic avian influenza (HPAI) virus (HPAIV), and H9 avian influenza viruses have been tested for efficacy in a number of animal models, including chickens, mice, and ferrets, and been shown to be efficacious and provide protection from challenge [48, 49] . Several rAd5 vectors have been explored for delivery of non-HA antigens, influenza nucleoprotein (NP) and matrix 2 (M2) protein [29, [50] [51] [52] . The efficacy of non-HA antigens has led to their inclusion with HA-based vaccines to improve immunogenicity and broaden breadth of both humoral and cellular immunity [53, 54] . However, as both CD8 + T cell and neutralizing antibody responses are generated by the vector and vaccine antigens, immunological memory to these components can reduce efficacy and limit repeated use [48] . | [
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How radiology departments respond to any infectious disease outbreak is determined primarily by the estimated risk of cross-infection to the staff and other patients. Appropriate precautions taken only by staff in direct contact with patients may be adequate when the risk is low. The strongest measures need to be implemented to limit the spread of the disease when the risk is high. With severe infectious diseases such as COVID-19, the highest level of infection control measures must be implemented; these include providing adequate standard protective equipment, training staff, and instituting proper emergency plans. Once a contagious infectious disease has been identified, the EMICT must consider four main areas of response: data gathering, collaboration, needs assessment, and expert advice [10]. Data gathering includes dissemination of up-to-date case definitions and information about confirmatory tests to all staff with direct patient contact to allow appropriate barrier precautions to be taken. | [
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Being entrusted with the resources and expectation to conceive, deliver and communicate dividends to society is both cherished and eagerly pursued at every stage of our careers. Nevertheless, the road to research translation is winding and is built on a foundation of basic research. Supporting industry-academia collaboration and nurturing talent and skills in the Indo-Pacific region are two of the four pillars of the National Innovation and Science Agenda. 2 These frame Australia's Medical Research and Innovation Priorities, which include antimicrobial resistance, global health and health security, drug repurposing and translational research infrastructure, 15 capturing many of the key elements of this CTI Special Feature. Establishing durable international relationships that integrate diverse expertise is essential to delivering these outcomes. To this end, NHMRC has recently taken steps under the International Engagement Strategy 16 to increase cooperation with its counterparts overseas. | [
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The general types of influenza vaccines available in the United States are trivalent inactivated influenza vaccine (TIV), quadrivalent influenza vaccine (QIV), and live attenuated influenza vaccine (LAIV; in trivalent and quadrivalent forms). There are three types of inactivated vaccines that include whole virus inactivated, split virus inactivated, and subunit vaccines. In split virus vaccines, the virus is disrupted by a detergent. In subunit vaccines, HA and NA have been further purified by removal of other viral components. TIV is administered intramuscularly and contains three or four inactivated viruses, i.e., two type A strains (H1 and H3) and one or two type B strains. TIV efficacy is measured by induction of humoral responses to the hemagglutinin (HA) protein, the major surface and attachment glycoprotein on influenza. | [
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We overexpressed NRIR in HUVEC and A549 cells using the pcDNA3.1 vector ( Figure 7B) . Importantly, overexpression of NRIR significantly suppressed IFITM3 mRNA and pre-mRNA levels and facilitated HTNV infection in HUVEC and A549 cells (Figures 7C-E) . These data suggest that lncRNA NRIR is a negative regulator of IFITM3 transcription. Hantaan virus is an enveloped, negative-sense RNA virus from the genus Hantavirus within the family Bunyaviridae. It causes HFRS, which is an important threat to public health worldwide. It is also a potential weapon for biological terrorism. Reservoir animals, usually rodents, are asymptomatic during persistent infection. | [
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Text: Microtubule severing enzymes are a family of AAA-ATPase proteins that participate in fundamental cellular processes such as mitosis, ciliary biogenesis and growth cone motility. In neurons this family is known to control such processes as axonal elongation 1 and synaptic development. 2 In addition, mutations in microtubule severing enzyme genes SPG4, KATNB1 and KATNAL2 are associated with hereditary spastic paraplegia, cerebral malformations and autism, respectively, [3] [4] [5] [6] and mutations in Fign cause a range of phenotypes in mice. 7 Currently the microtubule severing enzyme KATNAL1 is poorly characterised and it is not yet understood how the enzyme functions in the nervous system. Recent evidence from genetic characterisation of human patients suggests that haploinsufficiency of KATNAL1 is linked with a number of symptoms including intellectual disability (ID) and craniofacial dysmorphologies. 8, 9 It is also notable that a very rare KATNAL1 mutation has been associated with schizophrenia 10 (http://atgu.mgh.harvard.edu/~spurcell/genebook/gene book.cgi?user = guest&cmd = verb-gene&tbox = KATNAL1) and that Peters syndrome and autism have both been associated with the chromosomal region containing the KATNAL1 locus. | [
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The onset-to-death distribution is also Gamma distributed with a mean of 18.8 days and a coefficient of va riation 0.45. ifrm is population averaged over the age structure of a given country. The infection-to-death distribution is therefore given by: um ~ ifrm ~ (Gamma(5.1,0.86) + Gamma(18.8,0.45)) Figure 6 shows the infection-to-death distribution and the resulting survival function that integrates to the infection fatality ratio. Figure 6: Left, infection-to-death distribution (mean 23.9 days). Right, survival probability of infected individuals per day given the infection fatality ratio (1%) and the infection-to-death distribution on the left. Using the probability of death distribution, the expected number of deaths dam, on a given day t, for country, m, is given by the following discrete sum: The number of deaths today is the sum of the past infections weighted by their probability of death, where the probability of death depends on the number of days since infection. 8.2 Infection model The true number of infected individuals, C, is modelled using a discrete renewal process. | [
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Because of its promising results and the need for a safer vaccine, this consensus DNA vaccine deserves further investigation. Determining longevity of protective effects of the vaccine and persistence of antibody and IFN-c responses could be the next step of investigation. Challenged studies of immunized mice must also be carried out. CHIKV mosquito-borne disease has caused massive outbreaks for at least half a century but is no longer confined to the www.plosntds.org developing nations. It began to encroach into the boundaries of the developing world. As a result, the NIAID has designated CHIKV as a Category C pathogen alongside the influenza and SARS-CoV viruses [3] . | [
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Infections that cause massive destruction of the epithelium, such as IFV, usually result in severe acute exacerbations with non-classical symptoms of chronic airway inflammatory diseases. Fortunately, annual vaccines are available to prevent IFV infections (Vasileiou et al., 2017; Zheng et al., 2018) ; and it is recommended that patients with chronic airway inflammatory disease receive their annual influenza vaccination as the best means to prevent severe IFV induced exacerbation. Another mechanism that viral infections may use to drive acute exacerbations is the induction of vasodilation or tight junction opening factors which may increase the rate of infiltration. Infection with a multitude of respiratory viruses causes disruption of tight junctions with the resulting increased rate of viral infiltration. This also increases the chances of allergens coming into contact with airway immune cells. For example, IFV infection was found to induce oncostatin M (OSM) which causes tight junction opening (Pothoven et al., 2015; Tian et al., 2018) . | [
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Moreover, studies have indicated that influenza virus infection promotes neutrophil apoptosis 47 , delaying virus elimination 48 . Phosphorylation of CEACAM1 ITIM motifs and activation of caspase-3 is critical for mediating anti-apoptotic events and for promoting survival of neutrophils 27 . This suggests that CEACAM1-mediated anti-apoptotic events may be important for the resolution of influenza virus infection in vivo, which can be further investigated through infection studies with Ceacam1-knockout mice. NK cells play a critical role in innate defense against influenza viruses by recognizing and killing infected cells. Influenza viruses, however, employ several strategies to escape NK effector functions, including modification of influenza hemagglutinin (HA) glycosylation to avoid NK activating receptor binding 49 . Homo-or heterophilic CEACAM1 interactions have been shown to inhibit NK-killing 25, 26 , and are thought to contribute to tumor cell immune evasion 50 . | [
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Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R 0) from the RP model to assess the transmissibility of the SARS-CoV-2. Results The value of R 0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. Conclusions Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea. Text: On 31 December 2019, the World Health Organization (WHO) China Country Office was informed of cases of pneumonia of unknown etiology (unknown cause) detected in Wuhan City, Hubei Province of China, and WHO reported that a novel coronavirus (2019-nCoV), which was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020, was identified as the causative virus by Chinese authorities on 7 January [1] . It is reported that the virus might be bat origin [2] , and the transmission of the virus might related to a seafood market (Huanan Seafood Wholesale Market) exposure [3, 4] . | [
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I also discuss alternative posttranslational and RNA-based antiviral approaches, designer vaccines, immunotherapy and the emerging field of neo-virology. 4 I anticipate international efforts in these areas over the coming decade will enable the tapping of useful new biological functions and processes, methods for controlling infection, and the deployment of symbiotic or subclinical viruses in new therapies and biotechnologies that are so crucially needed. Upon infection, pathogens stimulate expression of numerous host inflammatory factors that support recruitment and activation of immune cells. On the flip side, this same process also causes immunopathology when prolonged or deregulated. 5 In their contribution to this Special Feature, Yoshinaga and Takeuchi review endogenous RNA-binding proteins (RBPs) that post-transcriptionally control expression of crucial inflammatory factors in various tissues and their potential therapeutic applications. 6 These RBPs include tristetraprolin and AUF1, which promote degradation of AU-rich element (ARE)-containing mRNA; members of the Roquin and Regnase families, which respectively promote or effect degradation of mRNAs harbouring stem-loop structures; and the increasingly apparent role of the RNA methylation machinery in controlling inflammatory mRNA stability. | [
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CHIKV infection is marked by severe joint pain, contorting its victims into unusual postures [6] . The disease gets its name from the Kimakonde vernacular language of Tanzania and Mozambique, and the word chikungunya means ''that which contorts or bends up'' and translates in Swahili to ''the illness of the bended walker'' [7, 8, 9] . In Africa, CHIKV is maintained in a sylvatic cycle among forest-dwelling Aedes spp. mosquitoes, wild primates, squirrels, birds, and rodents ( Figure 1 ) [10] . In Asia, the disease is vectored by Ae. aegypti and Ae. albopictus [11] . | [
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The orf8 protein sequences used in the analysis derived from early phase SARS-CoV that includes full-length orf8 (human SARS-CoV GZ02), the mid-and late-phase SARS-CoV that includes the split orf8b (human SARS-CoV Tor2), civet SARS-CoV (paguma SARS-CoV), two bat SARS-related-CoV containing full-length orf8 (bat-CoV YNLF_31C and YNLF_34C), 2019-nCoV, the other two closest bat SARS-related-CoV to 2019-nCoV SL-CoV ZXC21 and ZC45), and bat SARS-related-CoV HKU3-1 ( Figure 5(A) ). As expected, orf8 derived from 2019-nCoV belongs to the group that includes the closest genome sequences of bat SARS-related-CoV ZXC21 and ZC45. Interestingly, the new 2019-nCoV orf8 is distant from the conserved orf8 or Figure 5(B) ) which was shown to trigger intracellular stress pathways and activates NLRP3 inflammasomes [26] , but this is absent in this novel orf8 of 2019-nCoV. Based on a secondary structure prediction, this novel orf8 has a high possibility to form a protein with an alpha-helix, following with a betasheet(s) containing six strands ( Figure 5(C) ). The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 (MG772934.1), and 82% with human SARS-CoV BJ01 2003 (AY278488) and human SARS-CoV Tor2 (AY274119). The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes (S, E, M, and N) were shown (Figure 6(A-E) ). | [
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In this study, markedly elevated IP-10 (92,809 pg ml −1 ) combined with the highest PCT level (74.4 pg ml −1 ) were quantified in the serum sample of a child who died, in whom S. pneumoniae (serotype 9 V) was identified in the blood (PCR and blood culture) and co-detected with Haemophilus influenzae type B in nasal aspirate. These observations suggest an interrelationship between co-detection, elevated serum IP-10 and the pathogenesis of pneumonia. Several limitations of this pilot translational study need to be acknowledged before concluding mixed infection is related to elevated IP-10 and disease severity. Indeed, although viral shedding (e.g., of HRV and HBoV) is common in asymptomatic children, we were unable to evaluate the levels of immunomodulators in the serum samples of a control group. Moreover, although the samples were collected within the first 24 hours after admission, only a single blood sample was processed for each patient. Therefore, a larger, longitudinal study on the etiology and severity of pneumonia will be necessary to confirm these results. | [
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We found that the overall nucleotide sequence identity was 71.3 and 80% for HMPV group A and B, respectively, the diversity between HMPV groups was greater at amino acid level for SH and G surface protein genes, and multiple subgroups co-circulated in various countries. Comparison of sequences between HMPV groups revealed variability in G protein length (219 to 241 amino acids) due to changes in the stop codon position. Genome-wide phylogenetic analysis showed congruence with the individual gene sequence sets except for F and M2 genes. CONCLUSION: This is the first genomic characterization of HMPV genomes from African patients. Text: Human metapneumovirus (HMPV) is a single-stranded RNA virus in the family Paramyxoviridae and closely related to human respiratory syncytial virus (RSV) [1] . HMPV causes respiratory disease similar to RSV, ranging from mild upper respiratory infection to bronchiolitis and pneumonia [2] . | [
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the European CDC, US CDC, USAID and WHO) to assist in predicting the likelihood that a particular virus will emerge and its associated impact, as well as prioritising the development of candidate human vaccine viruses. 2 These tools allow continual reassessment as new data become available and provide an objective, transparent process with which to make resource allocation and pandemic planning decisions. In February 2013, China detected the first human cases of H7N9 infection in severely ill patients with pneumonia. 3 As of May 22, 2014 , there have been 446 confirmed H7N9 cases in China resulting in 163 deaths. 4 The cases have occurred mainly during two waves (weeks [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] 2013 and week 40, 2013week 20, 2014) , 4 of which 85% had prior exposure to poultry or contaminated live poultry markets. The median time from poultry exposure to disease onset was 5 days, whereas the median time from illness onset to hospital admission, ARDS development, antiviral therapy and death was 5, 6Á8, 7 and 14 days, respectively. | [
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Such an approach may be clinically significant due to the current scarcity of antiviral drugs for the management of viral-induced exacerbations. This will improve the quality of life of patients with chronic airway inflammatory diseases. Once the link between viral infection and acute exacerbations of chronic airway inflammatory disease was established, there have been many reports on the mechanisms underlying the exacerbation induced by respiratory viral infection. Upon infecting the host, viruses evoke an inflammatory response as a means of counteracting the infection. Generally, infected airway epithelial cells release type I (IFNα/β) and type III (IFNλ) interferons, cytokines and chemokines such as IL-6, IL-8, IL-12, RANTES, macrophage inflammatory protein 1α (MIP-1α) and monocyte chemotactic protein 1 (MCP-1) (Wark and Gibson, 2006; Matsukura et al., 2013) . These, in turn, enable infiltration of innate immune cells and of professional antigen presenting cells (APCs) that will then in turn release specific mediators to facilitate viral targeting and clearance, including type II interferon (IFNγ), IL-2, IL-4, IL-5, IL-9, and IL-12 (Wark and Gibson, 2006; Singh et al., 2010; Braciale et al., 2012) . | [
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In the current study, we propose an improved ANFIS model based on a modified flower pollination algorithm (FPA) using the salp swarm algorithm (SSA). The FPA is an optimization algorithm proposed by Yang [38] , which was inspired by the flow pollination process of the flowering plants. The FPA was employed in various optimization applications, for example to estimate solar PV parameter [39, 40] , solving sudoku puzzles [41] , feature selection [42] , antenna design [43] , and other applications [44] [45] [46] [47] . Moreover, SSA is also an optimization algorithm proposed by Mirjalili et al. [48] inspired by the behavior of salp chains. In recent years, the SSA was utilized to solve different optimization problems, such as feature selection [49, 50] , data classification [51] , image segmentation [52] , and others [53, 54] . | [
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These large-scale non-pharmaceutical interventions vary between countries but include social distancing (such as banning large gatherings and advising individuals not to socialize outside their households), border closures, school closures, measures to isolate symptomatic individuals and their contacts, and large-scale lockdowns of populations with all but essential internal travel banned. Understanding firstly, whether these interventions are having the desired impact of controlling the epidemic and secondly, which interventions are necessary to maintain control, is critical given their large economic and social costs. The key aim ofthese interventions is to reduce the effective reproduction number, Rt, ofthe infection, a fundamental epidemiological quantity representing the average number of infections, at time t, per infected case over the course of their infection. Ith is maintained at less than 1, the incidence of new infections decreases, ultimately resulting in control of the epidemic. If Rt is greater than 1, then infections will increase (dependent on how much greater than 1 the reproduction number is) until the epidemic peaks and eventually declines due to acquisition of herd immunity. In China, strict movement restrictions and other measures including case isolation and quarantine began to be introduced from 23rd January, which achieved a downward trend in the number of confirmed new cases during February, resulting in zero new confirmed indigenous cases in Wuhan by March 19th. | [
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Several studies have demonstrated the effectiveness and ease of using Listeria monocytogenes to deliver heterologous vaccine antigens and DNA vaccines Jensen et al., 1997; Johnson et al., 2011; Peters et al., 2003; Shen et al., 1995; Yin et al., 2011) . Similarly, various viral vectors have been successfully tested for their capability to deliver heterologous vaccine antigens, and this generally results in the induction of strong CTL immune responses. In the veterinary field, there are numerous viral vector vaccines that are currently licensed for use in livestock and domesticated animals. These recombinant vaccines are based on both DNA viruses (such as fowlpox virus-based vaccines which target avian influenza virus and fowlpox virus, or vaccinia virusbased vectors against the rabies virus in wildlife) and RNA viruses [such as Newcastle disease virus-based vaccines to be used in poultry or yellow fever virus (YFV)-based vaccines to be used in horses against West Nile virus] (Draper & Heeney, 2010) . Based on the safety record in the veterinary field, many viruses have been studied for human use as a vector in vaccine development (Beukema et al., 2006; Esteban, 2009; Schirrmacher & Fournier, 2009; Stoyanov et al., 2010; Weli & Tryland, 2011) . Amongst them, YFV (YF-17D strain) was the first to be licensed for use in humans, where the cDNAs encoding the envelope proteins of YFV were replaced with the corresponding genes of an attenuated Japanese encephalitis virus strain, SA14-14-2 (Appaiahgari & Vrati, 2010; Rollier et al., 2011) . | [
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We further evaluated the innate immune recognition of EAP, as this process is regulated primarily Dectin-1 and mannose receptor (MR). These results indicate that EAP may have immunomodulatory properties and a potential prophylactic effect against H5N1 influenza infection. Our investigation suggests an alternative strategy for the development of novel antiinfluenza agents and benefits of E. adenophorum products. Text: Highly pathogenic H5N1 subtype influenza virus can be transmitted directly from poultry to human and cause acute respiratory infections. Pandemic influenza virus H5N1 posed a worldwide threat to the public health because of rapid spread and high pathogenicity [1, 2] . The symptoms in animals or humans infected with H5N1 include fever, encephalitis, pneumonia, and severe acute respiratory syndrome (SARS) [3, 4] . | [
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The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. | [
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We used percentage of land under rice cultivation as a measure of extent. Rice cropping intensity is also a known risk factor [11, 17, 37] . We used the mean number of rice crops per year as a measure of intensity. The extent of aquaculture is a known risk factor [10] , possibly because water bodies offer routes for transmission and persistence of the virus. The percentage of land under aquaculture was used as a metric. Proximity to water bodies increases the risk of outbreaks [47, [50] [51] [52] , possibly by increasing the chance of contact between wild water birds and domestic poultry. | [
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The nature of interactions between hantavirus pathogen-associated molecular patterns (PAMP) with the pattern recognition receptors (PRR) of susceptible endothelial cells are beginning to be clarified. The prototypical HTNV appears to be recognized by TLR-3 [43] . Such an infection has consequences such as increased expression of HLA-DR in dendritic cells [66] and differentiation of monocytes toward dendritic cells [67] . (2) Direct viral effects. The observed correlation between viral load and disease severity leaves the possibility open that hantavirus particles or RNA can themselves have toxic effects on cells or on signaling. Some investigators have favored direct viral toxicity, acting through the inhibition of endothelial cell barrier function, as an explanation for much of the capillary leak, although there is widespread agreement that multiple mechanisms that mediate pathogenesis likely operate simultaneously in the affected patient [68] . | [
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Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005–07 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine. In this review, we summarize the evidence supporting these concepts. | [
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In the developed world, viruses are already the most common pathogens causing diarrhea [3] . Although viruses infecting humans had already been described since 1901 [4] and viruses were suspected to play a role in diarrhea, it lasted until 1972, when the first virus causing gastroenteritis (norovirus) was identified in an outbreak of diarrhea in Norwalk (California, United States) [5] . Shortly after the discovery of norovirus several other viruses causing gastroenteritis were discovered: rotavirus in epithelial cells of children with gastroenteritis [6] , astrovirus in infantile diarrhea cases [7] , enteric adenoviruses in the feces of children with acute diarrhea [8] , and sapovirus during an outbreak of gastroenteritis in an orphanage in Sapporo, Japan [9] . All these viruses spread via the fecal-oral route through person-to-person transmission and are described in more detail below. Noroviruses are part of the family Caliciviridae and outbreaks of norovirus gastroenteritis have been reported in cruise ships, health care settings, schools, and in the military, but norovirus is also responsible for around 60% of all sporadic diarrhea cases (diarrhea cases where an enteropathogen could be found), reviewed in the literature [10, 11] . The pathogenesis of norovirus infection has been tested in vivo. | [
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More recently, peptide-displaying phage have been used in attempts to generate therapeutic antibody responses for chronic diseases, cancer, immunotherapy, and immunocontraception. Immunization with phage displaying Alzheimer's disease β-amyloid fibril peptides elicited anti-aggregating antibodies in mice and guinea pigs (Frenkel et al., 2000 (Frenkel et al., , 2003 Esposito et al., 2008; Tanaka et al., 2011) , possibly reduced amyloid plaque formation in mice (Frenkel et al., 2003; Solomon, 2005; Esposito et al., 2008) , and may have helped maintain cognitive abilities in a transgenic mouse model of Alzheimer's disease (Lavie et al., 2004) ; however, it remains unclear how such antibodies are proposed to cross the blood-brain barrier. Yip et al. (2001) found that antibodies raised in mice against an ERBB2/HER2 peptide could inhibit breast-cancer cell proliferation. Phage displaying peptide ligands of an anti-IgE antibody elicited antibodies that bound purified IgE molecules (Rudolf et al., 1998) , which may be useful in allergy immunotherapy. Several strategies for phage-based contraceptive vaccines have been proposed for control of animal populations. | [
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Rotavirus is widely distributed in animals, which act as sources of rotavirus emergent strains, with these animals acting in the transmission between species and through reassortment leading to the emergence of new strains which have been reported in human infections [9] [10] [11] [12] . The rotavirus (RV) belongs to the Reoviridae family and comprises nine species known as Rotavirus group A to I, with a recent proposal of the J species [13, 14] . Rotavirus A (RVA) is widespread worldwide and predominantly infects humans, bovines and other mammal species, as well as birds [15] . They have a double-stranded ribonucleic acid (dsRNA) genome, divided into 11 segments coding for structural proteins (VP1-VP4, VP6 and VP7) and nonstructural (NSP1-NSP5/NSP6) proteins [16, 17] . There are records of a close relationship between Amazonian wildlife and human populations [18] , and this interaction is the effect of anthropogenic urbanization activities that result in the deforestation of forest areas, causing the degradation of previously isolated sites such as caves and small caves, a continuous and nature progressive process that has led not only to changes in wildlife habitats but also to a greater relationship with human populations in rural and urban environments, contributing to the occurrence and emergence of diseases different from what normally occurs in endemic regions [19] [20] [21] [22] . Although the results of RVA have already been described globally [12, [23] [24] [25] [26] [27] [28] [29] [30] , in Brazil, the occurrence, diversity and role of rotavirus in these animals are still poorly studied, considering the large number of present species [4, [31] [32] [33] [34] . | [
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Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID), the ‘convergence model’ was proposed to explain the multifactorial causality of disease emergence. The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors. We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. | [
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In general, SSA is employed to improve FPA to avoid its drawbacks (i.e., getting trapped at the local optima). The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization (WHO) official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error (MAPE), Root Mean Squared Relative Error (RMSRE), Root Mean Squared Relative Error (RMSRE), coefficient of determination ( R 2 ), and computing time. Furthermore, we tested the proposed model using two different datasets of weekly influenza confirmed cases in two countries, namely the USA and China. The outcomes also showed good performances. | [
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Retrospective analysis of nosocomial viral gastroenteritis in a pediatric hospital revealed that in 67% of the cases torovirus could be detected [35] . However, only a limited number of studies report the detection of torovirus and therefore the true pathogenesis and prevalence of this virus remains elusive. Picobirnaviruses belong to the Picobirnaviridae and were first detected in the feces of children with gastroenteritis [36] . Since the initial discovery, the virus has been detected in fecal samples of several animal species, and it has been shown that the viruses are genetically highly diverse without a clear species clustering, reviewed in the literature [37] . This high sequence diversity has also been observed within particular outbreaks of gastroenteritis [38, 39] , limiting the likelihood that picobirnaviruses are actually causing outbreaks, as no distinct single source of infection can be identified. In 1907 the first tissue culture system was developed which was regarded as the golden standard for virus detection for a long time, reviewed in the literature [40] . | [
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We used air travel volume estimates from Wuhan, China, to international destinations and a generalized linear regression model to identify locations that could have undetected imported cases. Our model can be adjusted to account for exportation of cases from other locations as the virus spreads and more information on importations and transmission becomes available. Early detection and appropriate control measures can reduce the risk for transmission in all locations. A novel coronavirus, later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in December 2019 in the city of Wuhan, capital of Hubei Province, China, where cases were first confirmed (1). During December 2019–February 2020, the number of confirmed cases increased drastically. Model estimates suggested that >75,000 persons were infected by January 25, 2020, and the epidemic had a doubling time of ≈6 days (2). | [
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Opening this CTI Special Feature, I outline ways these issues may be solved by creatively leveraging the so-called 'strengths' of viruses. Viral RNA polymerisation and reverse transcription enable resistance to treatment by conferring extraordinary genetic diversity. However, these exact processes ultimately restrict viral infectivity by strongly limiting virus genome sizes and their incorporation of new information. I coin this evolutionary dilemma the 'information economy paradox'. Many viruses attempt to resolve this by manipulating multifunctional or multitasking host cell proteins (MMHPs), thereby maximising host subversion and viral infectivity at minimal informational cost. 4 I argue this exposes an 'Achilles Heel' that may be safely targeted via host-oriented therapies to impose devastating informational and fitness barriers on escape mutant selection. | [
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In theory, the viral generation rate (number of viral RNA copies exhaled per minute) can be predicted by quantification of the exhaled viral load. Then, an estimation of the RNA copies per litre exhaled air or per minute can be calculated. Quantification of the exhaled InfB would allow us to predict the generation rate for this virus. Due to insufficient sample volume, we could not determine the number of RNA copies in the sample. Collection of exhaled breath condensates is a novel and non-invasive method for obtaining samples of the upper respiratory tract. The collection of EBC is easy to perform and can be conducted in a home environment. | [
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A meta-analysis of the risk of long-term outcomes after childhood pneumonia categorized chronic respiratory sequelae into major (restrictive lung disease, obstructive lung disease, bronchiectasis) and minor (chronic bronchitis, asthma, abnormal pulmonary function) groups [9] . The risk of developing at least one of the major sequelae was estimated as 6% after an ambulatory pneumonia event and 14% after an episode of hospitalized pneumonia. Because respiratory diseases affect almost 1 billion people globally and are a major cause of mortality and morbidity [10] , childhood pneumonia might contribute to substantial morbidity across the life course. Chest radiologic changes have been considered the gold standard for defining a pneumonia event [11] because clinical findings can be subjective and clinical definitions of pneumonia can be nonspecific. In 2005, to aid in defining outcomes of pneumococcal vaccine studies, the World Health Organization's (WHO) standardized chest radiograph description defined a group of children who were considered most likely to have pneumococcal pneumonia [12] . The term "end-point consolidation" was described as a dense or fluffy opacity that occupies a portion or whole of a lobe, or the entire lung. | [
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For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use. | [
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Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity. Text: Emerging pathogens cause new or previously unrecognized diseases, and among them, emerging zoonotic diseases are a major concern among scientists studying infectious diseases at different spatial and temporal scales [1, 2] . Changes in biotic and abiotic conditions may alter population disease dynamics and lead to the emergence of zoonotic infections [3] [4] [5] [6] . During the last decades, several outbreaks of emerging and re-emerging viral pathogens have occurred, affecting both purely-local and worldwide/pandemic involvement of human populations. Among the conspicuous examples are influenza A, Ebola virus, hepatitis C virus, severe adult respiratory distress (SARS), coronavirus, and human immunodeficiency virus, which challenge prevention and control measures of public health systems [7] . | [
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Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions, https://wwwnc.cdc.gov/eid/article/26/7/20-0250_article Volume 26, Number 7—July 2020 Research Pablo Martinez De Salazar1Comments to Author , René Niehus, Aimee Taylor1, Caroline O’Flaherty Buckee, and Marc LipsitchComments to Author Author affiliations: Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Suggested citation for this article Abstract Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exported from mainland China could lead to self-sustained outbreaks in other countries. By February 2020, several countries were reporting imported SARS-CoV-2 cases. To contain the virus, early detection of imported SARS-CoV-2 cases is critical. We used air travel volume estimates from Wuhan, China, to international destinations and a generalized linear regression model to identify locations that could have undetected imported cases. Our model can be adjusted to account for exportation of cases from other locations as the virus spreads and more information on importations and transmission becomes available. | [
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nan Text: Over 168 million people across 50 countries are estimated to need humanitarian assistance in 2020 [1] . Response to epidemics in complex humanitarian crisessuch as the recent cholera epidemic in Yemen and the Ebola epidemic in the Democratic Republic of Congois a global health challenge of increasing scale [2] . The thousands of Yemeni and Congolese who have died in these years-long epidemics demonstrate the difficulty of combatting even well-known pathogens in humanitarian settings. The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may represent a still greater threat to those in complex humanitarian crises, which lack the infrastructure, support, and health systems to mount a comprehensive response. Poor governance, public distrust, and political violence may further undermine interventions in these settings. Populations affected by humanitarian crises are expected to be particularly susceptible to COVID-19, the disease caused by SARS-CoV-2, due to displacement, crowded housing, malnutrition, inadequate water, sanitation, and hygiene (WASH) tools, and stigmatization. | [
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Upon activation, the NLRP3 is recruited to the mitochondria via association with mitochondrial antiviral signaling (MAVS) or mitofusin 2 expressed on the outer mitochondrial membrane Subramanian et al., 2013) ; these molecules then recruit the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1 to form the NLRP3 inflammasome. This event activates the downstream molecule, caspase-1, which catalyzes the proteolytic processing of pro-IL-1β and pro-IL-18 into their active forms and stimulates their secretion (Kayagaki et al., 2015; Shi et al., 2015) . It is increasingly evident that NLRP3 detects RNA viruses by sensing the cellular damage or distress induced by viroporins (Ichinohe et al., 2010; Ito et al., 2012; Triantafilou et al., 2013; Nieto-Torres et al., 2015) , transmembrane pore-forming proteins, encoded by certain RNA viruses; these proteins alter membrane permeability to ions by forming membrane channels (Tan et al., 2005; Chen and Ichinohe, 2015) . A recent study shows that the SARS-CoV E protein, which comprise only 76 amino acids, forms Ca 2+ -permeable ion channels and activates the NLRP3 inflammasome (Nieto-Torres et al., 2015) . Although the E and 3a proteins of SARS-CoV, which comprise 274 amino acids and contain three transmembrane domains (Zeng et al., 2004; Lu et al., 2006) , are thought to act as Na + /K + and K + channels, respectively (Wilson et al., 2004; Lu et al., 2006; Torres et al., 2007; Parthasarathy et al., 2008; Pervushin et al., 2009; Wang et al., 2011) , the role of the 3a protein in activating the NLRP3 inflammasome remains unknown. Here, we examined the role of the 3a protein in activating the NLRP3 inflammasome. | [
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The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. | [
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All three cell lines were challenged with all three viruses at two multiplicities of infection (MOI): 0.001 and 0.0001. Between 18 and 39 trials were run at each cell-virus-MOI combination, excepting rVSV-MARV infections on PaKiT01 cells at MOI = 0.001, for which only eight trials were run (see Materials and methods; Figure 1 -figure supplements 1-3, Supplementary file 1). Because plaque assays restrict viral transmission neighbor-to-neighbor in two-dimensional cellular space (Howat et al., 2006) , we were able to track the spread of GFP-expressing virus-infected cells across tissue monolayers via inverted fluorescence microscopy. For each infection trial, we monitored and re-imaged plates for up to 200 hr of observations or until total monolayer destruction, processed resulting images, and generated a time series of the proportion of infectious-cell occupied plate space across the duration of each trial (see Materials and methods). We used generalized additive models to infer the time course of all cell culture replicates and construct the multi-trial dataset to which we eventually fit our mechanistic transmission model for each cell line-virus-specific combination ( Figure 1; Figure 1 -figure supplements 1-5). All three recombinant vesicular stomatitis viruses (rVSV-G, rVSV-EBOV, and rVSV-MARV) infected Vero, RoNi/7.1, and PaKiT01 tissue cultures at both focal MOIs. | [
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7 They also discuss their recent work revealing how two IFN-cinducible factors exhibit broad-spectrum inhibition of IAV, measles (MV), zika (ZikV) and HIV by suppressing furin activity. 8 Over the coming decade, I expect to see an ever-finer spatiotemporal resolution of host-oriented therapies to achieve safe, effective and broad-spectrum yet costeffective therapies for clinical use. The increasing abundance of affordable, sensitive, high-throughput genome sequencing technologies has led to a recent boom in metagenomics and the cataloguing of the microbiome of our world. The MinION nanopore sequencer is one of the latest innovations in this space, enabling direct sequencing in a miniature form factor with only minimal sample preparation and a consumer-grade laptop computer. Nakagawa and colleagues here report on their latest experiments using this system, further improving its performance for use in resource-poor contexts for meningitis diagnoses. 9 While direct sequencing of viral genomic RNA is challenging, this system was recently used to directly sequence an RNA virus genome (IAV) for the first time. | [
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These results confirm the presence of broadly cross-neutralizing antibodies already reported using the HCV pseudoparticles system. CONCLUSION: This study presents a simple, specific and reproducible cell culture-based assay for determination of HCV-neutralizing antibodies in human sera. The assay should be an important tool for gauging the relationship between the neutralizing antibodies response and viral load kinetics in acutely or chronically infected patients and for investigating the possible eradication or prevention of HCV infection by neutralizing antibodies. Text: Hepatitis C virus (HCV, a member of the Flaviviridae family) is an enveloped, positive-stranded RNA virus that preferentially replicates in hepatocytes. At least 170 million people worldwide are persistently infected with hepatitis C virus. Chronic HCV infection is associated with a significant risk of progression to cirrhosis and hepatocellular carcinoma [1] . | [
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The virus may be present in anal swabs or blood of patients when oral swabs detection negative. In SARS-CoV and MERS-CoV infected patients, intestinal infection was observed at later stages of infection [7] [8] [9] . However, patients infected with 2019-nCoV may harbour the virus in the intestine at the early or late stage of disease. It is also worth to note none of the patients with viremia blood had positive swabs. These patients would likely be considered as 2019-nCoV negative through routine surveillance, and thus pose a threat to other people. In contrast, we found viral antibodies in near all patients, indicating serology should be considered for 2019-nCoV epidemiology. | [
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However, the low copy number of pIII-displayed proteins, as well as potentially unwanted phage-associated adjuvanticity, can make display of recombinant proteins by phage a suboptimal vaccine choice. Although our understanding of the immune response against the filamentous phage pales in comparison to classical model antigens such as ovalbumin, recent work has begun to shed light on the immune mechanisms activated in response to phage vaccination (Figure 1) . The phage particle is immunogenic without adjuvant in all species tested to date, including mice (Willis et al., 1993) , rats (Dente et al., 1994) , rabbits (de la Cruz et al., 1988) , guinea pigs (Frenkel et al., 2000; Kim et al., 2004) , fish (Coull et al., 1996; Xia et al., 2005) , non-human primates (Chen et al., 2001) , and humans (Roehnisch et al., 2014) . Various routes of immunization have been employed, including oral administration (Delmastro et al., 1997) as well as subcutaneous (Grabowska et al., 2000) , intraperitoneal (van Houten et al., 2006) , intramuscular (Samoylova et al., 2012a) , intravenous (Vaks and Benhar, 2011) , and intradermal injection (Roehnisch et al., 2013) ; no published study has directly compared the effect of administration route on filamentous phage immunogenicity. Antibodies are generated against only three major sites on the virion: (i) the surface-exposed N-terminal ∼12 residues of the pVIII monomer lattice (Terry et al., 1997; Kneissel et al., 1999) ; (ii) the N-terminal N1 and N2 domains of pIII (van Houten et al., 2010) ; and (iii) bacterial lipopolysaccharide (LPS) embedded in the phage coat (Henry et al., 2011) . In mice, serum antibody titers against the phage typically reach 1:10 5 -1:10 6 after 2-3 immunizations, and are maintained for at least 1 year postimmunization (Frenkel et al., 2000) . | [
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Sex-stratified models showed that high birth weight heifers treated with ZM gained more than placebo-treated heifers of the same birth weight, which suggests a dose-response effect rather than a true sex-specific effect of ZM on ADG. Cox regression showed that ZM and ZS-treated calves had a 14.7% (P = 0.015) and 13.9% (P = 0.022) reduced hazard of diarrhea, respectively, compared to placebo-treated calves. Calves supplemented for at least the first five days of diarrhea with ZM and ZS had a 21.4% (P = 0.027) and 13.0% (P = 0.040) increased hazard of cure from diarrhea, respectively, compared to placebo-treated calves. Logistic regression showed that the odds of microbiological cure at diarrhea resolution for rotavirus, C. parvum, or any single fecal pathogen was not different between treatment groups. Zinc supplementation delayed diarrhea and expedited diarrhea recovery in pre-weaned calves. Additionally, zinc improved weight gain differentially in bulls compared to heifers, indicating a research need for sex-specific dosing. | [
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Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. | [
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As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI. Text: Influenza like-illness (ILI) or acute respiratory infections can be caused by several types of respiratory viruses or bacteria in humans [1] . Influenza viruses, Respiratory Syncytial viruses (RSV) and Parainfluenza viruses are identified as major viruses mostly responsible for ILI and pneumonia in several studies [2] . However practitioners cannot diagnose the infection without a biological test confirmation. Unfortunately, these infections causes are identified in less than 50% [3] . Réunion Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean (Latitude: 21°05.2920 S Longitude: 55°36.4380 E.). | [
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Oral administration with B. subtilis-RC could effectively reduce the plaque-forming ability of PEDV (P<0.01) compared with other two groups in Figure 7 . This revealed that B. subtilis-RC could stimulate high level of PEDV neutralizing antibodies against PEDV infection. Amidst the PEDV outbreak, various vaccines have been developed to control diseases and the effects are unsatisfactory. Oral vaccines can induce more robust mucosal immunity than injectable counterparts [32] . Therefore, oral immunization has appeared as an effective strategy for controlling PEDV outbreak [33] . It is now clear that effective mucosal immune response requires serum IgG and mucosal SIgA [34] . | [
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This is the first molecular and serological study on this virus after the initial identification of 2019-NCoV from 7 patients diagnosed with unidentified viral pneumonia [5] . We detected the virus in oral swabs, anal swabs and blood, thus infected patients can potentially shed this pathogen through respiratory, fecal-oral or body fluid routes. In addition, we successfully applied serology test a large population and showed which could greatly improved detection positive rate. We show that the current strategy for the detection of viral RNA in oral swabs used for 2019-nCoV diagnosis is not perfect. The virus may be present in anal swabs or blood of patients when oral swabs detection negative. In SARS-CoV and MERS-CoV infected patients, intestinal infection was observed at later stages of infection [7] [8] [9] . | [
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Dull substernal chest pain and rash were also observed in two patients. All patients had dyspnea. The mean time from onset to dyspnea was 5 days (range, 1 to 10 days). After the onset of dyspnea, patients usually progressed to respiratory failure or hypoxemia. The mean time from onset to ICU admission was 9.6 days (range, 8 to 11 days) ( Table 1) . All patients had tachypnea when admitted to the ICU, with a mean rate of 43 breaths per minute (range = 38 to 52). | [
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The latter CTLs mediate a delayed-type hypersensitivity reaction (Fang et al., 2005; Del Pozzo et al., 2010) . The phage particle is self-adjuvanting through multiple mechanisms. Host cell wall-derived LPS enhances the virion's immunogenicity, and its removal by polymyxin B chromatography reduces antibody titers against phage coat proteins (Grabowska et al., 2000) . The phage's singlestranded DNA genome contains CpG motifs and may also have an adjuvant effect. The antibody response against the phage is entirely dependent on MyD88 signaling and is modulated by stimulation of several Toll-like receptors (Hashiguchi et al., 2010) , indicating that innate immunity plays an important but largely uncharacterized role in the activation of anti-phage adaptive immune responses. Biodistribution studies of the phage after intravenous injection show that it is cleared from the blood within hours through the reticuloendothelial system (Molenaar et al., 2002) , particularly of the liver and spleen, where it is retained for days (Zou et al., 2004) , potentially activating marginal-zone B-cell responses. | [
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Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus (HA closely related to the avian influenza A(H7N9) virus) and a H1N1(09)pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection. CONCLUSION: A nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials. Text: The periodic appearance of new influenza variants poses a worldwide pandemic threat. Since the emergence of the new A(H7N9) virus, more than 400 human cases were reported to the WHO with a mortality rate of more than 35%. Most patients with A(H7N9) infections had contact with poultry or visited live animal markets. | [
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We therefore used this new method to set up a retrospective study using swabs collected by sentinel GPs from 2011 to 2012. The main objective of our study was to characterize respiratory pathogens responsible for ILI consultations in sentinel GPs in 2011 and 2012. Secondary objectives were to highlight seasonal trends on respiratory pathogens circulation and to describe occurrence of co-infections, especially during the flu season. ILI was defined as a sudden onset of fever more than 38 degrees Celsius and cough, associated or not with other symptoms such as breathing difficulty, headache, etc. Every week, all GPs of the sentinel network were encouraged to collect a nasal swab from the first two patients who presented ILI since less than three days. After being tested for influenza viruses, the 994 swabs collected in 2011 and 2012 are frozen at -80°C at the university hospital center (CHU) laboratory. | [
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Hence, it is important to identify the exact mechanisms underpinning viral exacerbations in susceptible subjects in order to properly manage exacerbations via supplementary treatments that may alleviate the exacerbation symptoms or prevent severe exacerbations. While the lower airway is the site of dysregulated inflammation in most chronic airway inflammatory diseases, the upper airway remains the first point of contact with sources of exacerbation. Therefore, their interaction with the exacerbation agents may directly contribute to the subsequent responses in the lower airway, in line with the "United Airway" hypothesis. To elucidate the host airway interaction with viruses leading to exacerbations, we thus focus our review on recent findings of viral interaction with the upper airway. We compiled how viral induced changes to the upper airway may contribute to chronic airway inflammatory disease exacerbations, to provide a unified elucidation of the potential exacerbation mechanisms initiated from predominantly upper airway infections. Despite being a major cause of exacerbation, reports linking respiratory viruses to acute exacerbations only start to emerge in the late 1950s (Pattemore et al., 1992) ; with bacterial infections previously considered as the likely culprit for acute exacerbation (Stevens, 1953; Message and Johnston, 2002) . | [
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Gender-based violence around latrines is an important deterrent for accessing latrine-adjacent handwashing stations, particularly for hand hygiene to prevent respiratory pathogen transmission. Evidence-based guidelines alone in complex humanitarian crises may not suffice during the emergence of the current SARS-CoV-2 pandemic. Without the adaptation of existing standards, mitigation plans will fall short of health and human rights obligations in outbreak response. Crisis-affected community engagement is integral in pandemic planning, in order to maximize the real-world effectiveness of efficacious interventions. Transparent and credible information-sharing mechanisms are increasingly essential when pandemics threaten vulnerable populations [10] . Diplomacy bridging long-standing mistrust of public health and biomedical interventions and facilitating engagement with contentious actors is a necessary component of effective health governance in complex crisis settings [2] . | [
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Although the compound decreased viral replication and shedding, it failed to show a significant reduction in the duration or severity of symptoms [40, 41] . A Protease inhibitor, rupintrivir thats prevents cleavage of viral proteins required for replication was tested in an HRV challenge trial. Rupintrivir was well tolerated and reduced viral loads and respiratory symptoms [36] . However, in studies of natural infection, it did not significantly affect viral loads or symptom severity [42] . Treatments such as zinc-containing products are now widely discredited as demonstrated by the withdrawal of a Cochrane report and JAMA editorial [43] [44] [45] . Current treatment of HRV infections primarily consists of over-the-counter (OTC) medicines to manage symptoms. | [
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In the present study, we designed a new artificial peptide, AP3 (Fig. 1a) , aiming to apply the "M-T hook" structure to stabilize the interaction of the artificial peptide with the hydrophobic pocket on the gp41 NHR trimer 17, 18 . After comprehensively studying its antiviral activity, biochemical property, crystal structure, functional mechanism, in vivo half-life and, for the first time, the effect of preexisting antibodies in the sera of HIV-infected patients, we found that the newly designed artificial peptide, AP3, exhibited improved antiviral activity, drug resistance profile and pharmacological properties over T20. Particularly, the preexisting antibodies in the sera of HIV-infected patients did not suppress, but enhanced the anti-HIV-1 activity of AP3. These results suggest that AP3 has potential for development as a new anti-HIV drug and confirm that this strategy can be used for designing artificial antiviral peptides against other enveloped viruses, such as SARS-CoV 19 , MERS-CoV 20 , and paramyxovirus 21 . AP3 inhibited HIV-1 infection with higher potency than T20. | [
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Split virus inactivated vaccines can induce neuraminidase (NA)-specific antibody responses [15] [16] [17] , and anti-NA antibodies have been associated with protection from infection in humans [18] [19] [20] [21] [22] . Currently, NA-specific antibody responses are not considered a correlate of protection [14] . LAIV is administered as a nasal spray and contains the same three or four influenza virus strains as inactivated vaccines but on an attenuated vaccine backbone [4] . LAIV are temperature-sensitive and cold-adapted so they do not replicate effectively at core body temperature, but replicate in the mucosa of the nasopharynx [23] . LAIV immunization induces serum antibody responses, mucosal antibody responses (IgA), and T cell responses. While robust serum antibody and nasal wash (mucosal) antibody responses are associated with protection from infection, other immune responses, such as CD8 + cytotoxic lymphocyte (CTL) responses may contribute to protection and there is not a clear correlate of immunity for LAIV [4, 14, 24] . | [
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In this study, we demonstrate for the first time, the potential functional impact of DC-SIGNR mutations on its expression in the placenta and in vertical transmission of HIV-1. We believe that the presence of DC-SIGNR at the placental endothelial cell surface may protect infants from HIV-1 infection by capturing virus and promoting its degradation/presentation. However, in placenta containing low levels of DC-SIGNR, HIV-1 would preferentially binds CCR5 on endothelial cells resulting in a loss of placental barrier integrity and enhanced passage of maternal HIV-1-infected cells in foetal circulation leading to MTCT of HIV-1. This mechanism may also apply to other vertically-transmitted pathogens known to interact with DC-SIGNR such as HIV-2, hepatitis C and dengue viruses and warrant further investigation. Associations between child DC-SIGNR exon 4 repeated region genotypes and mother-to-child HIV-1 transmission.CI, Confidence interval; N, number; NA; not applicable; OR, odds ratio a P-value as determined by the Chi-square test. b Comparison between genotype and all others. | [
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Frequent displacement and limited contact information may prevent effective contact tracing. Finally, intractable structural challenges such as overcrowding limit the implementation of both quarantine of those exposed and isolation of those who are ill. Given these increased vulnerabilities, humanitarian crises should be viewed as a priority for national and international bodies that seek to combat this unfolding pandemic. Resources must be identified to protect healthcare workers, develop and deploy rapid testing, improve surveillance, and enact quarantine and isolation of contacts and cases. To mitigate the impact of COVID-19 on crisesaffected populations, governments and agencies will implement the familiar, global evidence-based approaches for combatting respiratory viruses. Respiratory hygiene is a highly effective public health intervention, supported by evidence demonstrating that the spread of respiratory viruses, such as SARS-CoV-2, can be prevented by hand hygiene, safe cough practice, and social distancing [4] . | [
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Of all participants, 764 (60.8%) were nurses, and 493 (39.2%) were physicians; 760 (60.5%) worked in hospitals in Wuhan, and 522 (41.5%) were frontline health care workers. A considerable proportion of participants reported symptoms of depression (634 [50.4%]), anxiety (560 [44.6%]), insomnia (427 [34.0%]), and distress (899 [71.5%]). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers (eg, median [IQR] Patient Health Questionnaire scores among physicians vs nurses: 4.0 [1.0-7.0] vs 5.0 [2.0-8.0]; P = .007; median [interquartile range {IQR}] Generalized Anxiety Disorder scale scores among men vs women: 2.0 [0-6.0] vs 4.0 [1.0-7.0]; P < .001; median [IQR] Insomnia Severity Index scores among frontline vs second-line workers: 6.0 [2.0-11.0] vs 4.0 [1.0-8.0]; P < .001; median [IQR] Impact of Event Scale–Revised scores among those in Wuhan vs those in Hubei outside Wuhan and those outside Hubei: 21.0 [8.5-34.5] vs 18.0 [6.0-28.0] in Hubei outside Wuhan and 15.0 [4.0-26.0] outside Hubei; P < .001). Multivariable logistic regression analysis showed participants from outside Hubei province were associated with lower risk of experiencing symptoms of distress compared with those in Wuhan (odds ratio [OR], 0.62; 95% CI, 0.43-0.88; P = .008). Frontline health care workers engaged in direct diagnosis, treatment, and care of patients with COVID-19 were associated with a higher risk of symptoms of depression (OR, 1.52; 95% CI, 1.11-2.09; P = .01), anxiety (OR, 1.57; 95% CI, 1.22-2.02; P < .001), insomnia (OR, 2.97; 95% CI, 1.92-4.60; P < .001), and distress (OR, 1.60; 95% CI, 1.25-2.04; P < .001). CONCLUSIONS AND RELEVANCE: In this survey of heath care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 in Wuhan and other regions in China, participants reported experiencing psychological burden, especially nurses, women, those in Wuhan, and frontline health care workers directly engaged in the diagnosis, treatment, and care for patients with COVID-19. | [
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Glycyrrhizin, a triterpene saponine, is a constituent of licorice root. It has been found to interfere with replication and/or cytopathogenic effect (CPE) induction of many viruses including respiratory viruses such as respiratory syncytial virus, SARS coronavirus, HIV, and influenza viruses [22] [23] [24] [25] [26] [27] [28] . Moreover, antiinflammatory and immunomodulatory properties were attributed to glycyrrhizin [26] . The severity of human H5N1 disease has been associated with hypercytokinaemia (''cytokine storm'') [29, 30] . Delayed antiviral plus immunomodulator treatment reduced H5N1-induced mortality in mice [31] . Therefore, antiinflammatory and immunomodulatory effects exerted by glycyrrhizin may be beneficial for treatment of H5N1. | [
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However, there were few public reports on the assessment of the effect of these policies and the level of knowledge, attitude and practice (KAP) associating with A/H1N1 among general population. It is well-known that confused comprehension and negative attitude towards the emerging communicable disease may lead to unnecessary worry and chaos, even excessive panic which would aggravate the disease epidemic [9] . For instance, during SARS epidemic from 2002 to 2004, the misconceptions and the excessive panic of Chinese public to SARS led the public resistant to comply with the suggested preventive measures such as avoiding public transportation, going to hospital when they were sick, which contributed to the rapid spread of SARS and resulted in a more serious epidemic situation, making China one of the worst affected countries with over 5327 cases and 439 deaths [10, 11] . In addition, the panic of infectious disease outbreak could cause huge economic loss, for example the economic loss of SARS has been estimated at $30-$100 billion in US, though less than 10,000 persons were infected [12] . SARS experience has demonstrated the importance of monitoring the public perception in disease epidemic control, which may affect the compliance of community to the precautionary strategies. Understanding related factors affecting people to undertake precautionary behavior may also help decision-makers take appropriate measures to promote individual or community health. | [
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Recent genomic research has revealed that there are 5 IFITM members in humans (IFITM1, 2, 3, 5 and 10) and 7 members in mice (IFITM1, 2, 3, 5, 6, 7, and 10). These proteins play roles in diverse biological processes, such as germ cell maturation during gastrulation (IFITM1-3) [3] [4] [5] , cell-to-cell adhesion (IFITM1) [6] [7] [8] , antiviral activity (IFITM1-3) [9] [10] [11] [12] [13] [14] [15] [16] [17] , and bone formation (IFITM5) [18] [19] [20] [21] [22] , although the detailed functions of IFITM6, 7, and 10 are unknown at present. In particular, IFITM3 has been a target of intensive studies on its activity against influenza A (H1N1) virus infection and internalization [9] [10] [11] [12] [13] [14] . In 2010, Dr. Yount and co-workers reported that the antiviral activity of IFITM3 is dependent on S-palmitoylation on the protein [10] . The S-palmitoylation [23] is a post-translational modification on proteins by C 16 saturated-fatty acids (palmitic acids) covalently attached to certain cysteine residues via a thioester linkage (Figure 1-B) . The modification is reversibly catalyzed by protein acyltransferases and acylprotein thioesterases, and confers unique properties to the protein, such as membrane binding and targeting, immunoreactivity, Amino-acid sequence alignment of IFITM5, IFITM1, IFITM2, and IFITM3 derived from mice. | [
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Gender-based violence around latrines is an important deterrent for accessing latrine-adjacent handwashing stations, particularly for hand hygiene to prevent respiratory pathogen transmission. Evidence-based guidelines alone in complex humanitarian crises may not suffice during the emergence of the current SARS-CoV-2 pandemic. Without the adaptation of existing standards, mitigation plans will fall short of health and human rights obligations in outbreak response. Crisis-affected community engagement is integral in pandemic planning, in order to maximize the real-world effectiveness of efficacious interventions. Transparent and credible information-sharing mechanisms are increasingly essential when pandemics threaten vulnerable populations [10] . Diplomacy bridging long-standing mistrust of public health and biomedical interventions and facilitating engagement with contentious actors is a necessary component of effective health governance in complex crisis settings [2] . | [
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Figure l: Intervention timings for the 11 European countries included in the analysis. For further details see Appendix 8.6. 2.1 Estimated true numbers of infections and current attack rates In all countries, we estimate there are orders of magnitude fewer infections detected (Figure 2) than true infections, mostly likely due to mild and asymptomatic infections as well as limited testing capacity. In Italy, our results suggest that, cumulatively, 5.9 [1.9-15.2] million people have been infected as of March 28th, giving an attack rate of 9.8% [3.2%-25%] of the population (Table 1). Spain has recently seen a large increase in the number of deaths, and given its smaller population, our model estimates that a higher proportion of the population, 15.0% (7.0 [18-19] million people) have been infected to date. Germany is estimated to have one of the lowest attack rates at 0.7% with 600,000 [240,000-1,500,000] people infected. | [
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Older people and people with severe chronic conditions should take special precautions because they are at higher risk of developing serious COVID-19 illness. If you are a healthcare provider, use your judgment to determine if a patient has signs and symptoms compatible with COVID-19 and whether the patient should be tested. Factors to consider in addition to clinical symptoms may include: Does the patient have recent travel from an affected area? Has the patient been in close contact with someone with COVID-19 or with patients with pneumonia of unknown cause? Does the patient reside in an area where there has been community spread of COVID-19? If you are a healthcare provider or a public health responder caring for a COVID-19 patient, please take care of yourself and follow recommended infection control procedures. | [
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However, these studies also indicate that downregulation of antigenspecific immune responses is highly dependent on dose and time. Leong et al. (2009) also demonstrated that the negative impact of vector-specific immune responses can also be countered by repeated immunization with the same vaccine and dose; this in effect leads to higher priming of naive T cells against the delivered antigen. Of course, such repeated vaccination may not be practicable in real-world situations. Despite the many advantages which viral vectoring can offer, pre-existing immunity is a major obstacle of many viralvectored vaccines, such as Ad serotype 5 or herpes simplex virus type 1 (HSV-1), where the rate of seroprevalence to these viruses is very high [40-45 % and 70 % (or more) of the US population, respectively] (Hocknell et al., 2002; Pichla-Gollon et al., 2009) . Vector-specific antibodies may impede the induction of immune responses to the vaccine-encoded antigens, as they may reduce the dose and time of exposure of the target cells to the vaccinated antigens (Pichla-Gollon et al., 2009; Pine et al., 2011) . | [
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