Influenza Virus Net is the web resource for anyone interested in influenza and flu pandemics. The objectives of Influenza Virus Net are to be the public and professional information resource for influenza and to serve as a network in the exchange of information and news related to influenza.

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae (the influenza viruses), that affects humans, birds and other mammals. The virus spreads easily from person to person. Influenza circulates worldwide and can affect anybody in any age group. Influenza causes annual epidemics that peak during winter in temperate regions. Influenza is a serious public health problem that causes severe illnesses and deaths for higher risk populations. The most common symptoms of the disease are chills, fever, sore throat, muscle pains, severe headache, coughing, weakness/fatigue and general discomfort. Sore throat, fever and coughs are the most frequent symptoms. In more serious cases, influenza causes pneumonia, which can be fatal, particularly for the young and the elderly. An influenza epidemic can take an economic toll through lost workforce productivity, and strain health services. Vaccination is the most effective way to prevent infection.

• Steer clear of flu with vigorous exercise - The Malay Mail Online
  Sat, 19 Apr 2014 09:31:
• Second wave of milder flu hitting Northeast - 46 Minutes Ago - The Herald Bulletin
  Sat, 19 Apr 2014 09:11:
• 9k doses of flu vaccine issued at Altnagelvin - Londonderry Today
  Sat, 19 Apr 2014 07:26:
• Surprise: Winter is Over but Not the Flu; polyDNA Recommends Talking to the ... - DigitalJournal.com
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• Flu Makes Easter Resurgence In New Jersey: Has It Affected You? - Patch.com
  Sat, 19 Apr 2014 07:08:
• Kevan Miller: (Flu) DNP Friday - Rotowire
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• Flu deaths reach 100 - Winston-Salem Journal
  Sat, 19 Apr 2014 00:38:
• Second wave of milder flu hitting Northeast US, CDC says - WDEF News 12
  Fri, 18 Apr 2014 23:44:
• Wikipedia Proves Useful for Tracking Flu - Tolerance
  Fri, 18 Apr 2014 22:33:
• After overcoming severe case, woman champions flu shots - Meriden Record-Journal
  Fri, 18 Apr 2014 22:25:

• PRO/AH/EDR> Avian influenza (52): Japan (KM) HPAI serotyped H5N8
  Thu, 17 Apr 2014 23:34:38
  Avian Influenza -- Japan
  The avian influenza found in chickens in Kumamoto Prefecture has been identified as the H5N8 virus, the agriculture ministry said Thursday [17 Apr 2014].
  The Agriculture, Forestry and Fisheries Ministry said it found H5N8 in samples from birds at a farm in Kumamoto where a surge in chicken deaths set off the culling Sunday and Monday [13-14 Apr 2014] of some 112 000 birds.
  This is the 1st discovery of the H5N8 virus in Japan. Cases of suspected H5N8 bird infections have been reported

• Determination of preventive behaviors for pandemic influenza A/H1N1 based on protection motivation theory among female high school students in Isfahan, Iran.
  Sharifirad G, Yarmohammadi P, Sharifabad MA, et al. Determination of preventive behaviors for pandemic influenza A/H1N1 based on protection motivation theory among female high school students in Isfahan, Iran. [Journal Article]J Educ Health Promot 2014.:7.Influenza A/H1N1 pandemic has recently threatened the health of world's population more than ever. Non-pharmaceutical measures are important to prevent the spread of influenza A/H1N1 and to prevent a pandemic. Effective influenza pandemic management requires understanding of the factors influencing preventive behavioral. This study reports on predictors of students' preventive behaviors for pandemic influenza A/H1N1 using variables based on the protection motivation theory (PMT).In a cross-sectional study, multiple-stage randomized sampling was used to select 300 female students in Isfahan who completed a questionnaire in December 2009. Data were collected using a self-report questionnaire based on PMT. The statistical analysis of the data included bivariate correlations, Mann-Whitney, Kruskal-Wallis, and linear regression.The mean age of participants was 15.62 (SE = 1.1) years old. Majority of participants were aware regarding pandemic influenza A/H1N1 (87.3%, 262 out of 300). Results showed that, protection motivation was highly significant relationship with preventive behavior and predicted 34% of its variance. We found all of the variables with the exception of perceived susceptibility, perceived severity, and response cost were related with protection motivation and explained 22% of its variance.Promotion of students' self-efficacy, and intention to protect themselves from a health threat should be priorities of any programs aimed at promoting preventive behaviors among students. It is also concluded that the protection motivation theory may be used in developing countries, like Iran, as a framework for prevention interventions in an attempt to improve the preventive behaviors of students.


• Construction of a Chimeric Secretory IgA and Its Neutralization Activity against Avian Influenza Virus H5N1.
  Li C, An X, Butt AM, et al. Construction of a Chimeric Secretory IgA and Its Neutralization Activity against Avian Influenza Virus H5N1. [Journal Article]J Immunol Res 2014.:394127.Secretory immunoglobulin A (SIgA) acts as the first line of defense against respiratory pathogens. In this assay, the variable regions of heavy chain (VH) and Light chain (VL) genes from a mouse monoclonal antibody against H5N1 were cloned and fused with human IgA constant regions. The full-length chimeric light and heavy chains were inserted into a eukaryotic expressing vector and then transfected into CHO/dhfr-cells. The chimeric monomeric IgA antibody expression was confirmed by using ELISA, SDS-PAGE, and Western blot. In order to obtain a dimeric secretory IgA, another two expressing plasmids, namely, pcDNA4/His A-IgJ and pcDNA4/His A-SC, were cotransfected into the CHO/dhfr-cells. The expression of dimeric SIgA was confirmed by using ELISA assay and native gel electrophoresis. In microneutralization assay on 96-well immunoplate, the chimeric SIgA showed neutralization activity against H5N1 virus on MDCK cells and the titer was determined to be 1 : 64. On preadministrating intranasally, the chimeric SIgA could prevent mice from lethal attack by using A/Vietnam/1194/04 H5N1 with a survival rate of 80%. So we concluded that the constructed recombinant chimeric SIgA has a neutralization capability targeting avian influenza virus H5N1 infection in vitro and in vivo.


• The characteristics of nucleocytoplasmic transport of H1N1 influenza A viruses nuclear export protein (NEP).
  Gao S, Wang S, Cao S, et al. The characteristics of nucleocytoplasmic transport of H1N1 influenza A viruses nuclear export protein (NEP). [JOURNAL ARTICLE]J Virol 2014 Apr 16.The influenza A virus nuclear export protein (NEP) plays crucial roles in the nuclear export of the viral ribonucleoprotein complex through the CRM1-mediated cellular protein transport system. However, the detailed mechanism of NEP nucleocytoplasmic trafficking remain incompletely understood. Here, we investigated the subcellular localization of NEP from two strains of H1N1 influenza A virus and found that 2009 swine-origin H1N1 influenza A virus A/California/04/2009 (CA04) NEP displayed a distinct cellular distribution pattern, forming unique nuclear aggregates, compared to A/WSN/33 (H1N1) (WSN) NEP. Characterization of the nucleocytoplasmic transport pathways of these two NEPs showed that they both enter the nucleus by passive diffusion but are exported through the nuclear export receptor chromosome region maintenance 1 (CRM1)-mediated pathway with different efficiencies. The two identified NESs on both NEPs functioned similarly despite differences in their amino acid sequences. Using a two-hybrid assay, we confirmed that the CA04 NEP interacts less efficiently with CRM1, and a threonine residue at position 48 is responsible for the nuclear aggregation. The present study revealed the dissimilarity in subcellular NEP transport processes between the 2009 pandemic (H1N1) influenza A virus CA04 and lab-adapted H1N1 virus WSN and uncovered the mechanism for this difference.Because the efficiency of the nucleocytoplasmic transport of viral components is often correlated with the viral RNA polymerase activity, propagation, and host range of influenza viruses, the present study investigated the subcellular localization of NEP from two strains of H1N1 influenza virus. We found that both the NEPs of A/California/04/2009 (H1N1) (CA04) and A/WSN/33 (H1N1) (WSN) enter the nucleus by passive diffusion but are exported with different efficiencies, which was caused by weaker binding activity between the CA04 NEP and CRM1. The results of the present study revealed characteristics of the nuclear import and export pathways of NEP and mechanism for the difference in cellular distribution of NEP between two H1N1 strains.


• ENHANCED VIRAL REPLICATION AND MODULATED INNATE IMMUNE RESPONSES IN INFANT AIRWAY EPITHELIUM FOLLOWING H1N1 INFECTION.
  Clay CC, Reader JR, Gerriets JE, et al. ENHANCED VIRAL REPLICATION AND MODULATED INNATE IMMUNE RESPONSES IN INFANT AIRWAY EPITHELIUM FOLLOWING H1N1 INFECTION. [JOURNAL ARTICLE]J Virol 2014 Apr 16.Influenza is the cause of significant morbidity and mortality in pediatric populations. The contribution of pulmonary host defense mechanisms to viral respiratory infection susceptibility in very young children is poorly understood. As a surrogate to compare mucosal immune responses for infant and adult lung, rhesus monkey primary airway epithelial cell cultures were infected with pandemic influenza A/H1N1 in vitro. Virus replication, cytokine secretion, cell viability and type I interferon (IFN) pathway PCR array profiles were evaluated for both infant and adult cultures. In comparison with adult cultures, infants showed significantly increased levels of H1N1 replication, reduced IFN-alpha protein synthesis and no difference in cell death following infection. Age-dependent differences in expression of multiple genes associated with the type I IFN pathway were observed in H1N1-infected cultures. To investigate the pulmonary and systemic response to H1N1 infection in early life, infant monkeys were inoculated with H1N1 by upper airway administration. Animals were monitored over a 14 day period for virus and parameters of inflammation. High H1N1 titers were recovered from airways at day 1, with viral RNA remaining detectable until day 9 post infection. Despite viral clearance, bronchiolitis and alveolitis persisted at day 14 post infection; histopathologic analysis revealed alveolar septal thickening and intermittent type II pneumocyte hyperplasia. Our overall findings are consistent with the known susceptibility of respiratory virus infection in pediatric populations and suggest that intrinsic developmental differences in airway epithelial cell immune function may contribute to the limited efficacy of host defense during early childhood.To the best of our knowledge, this study represents the first report of intrinsic developmental differences in infant airway epithelial cells that may contribute to increased susceptibility of the host to respiratory virus infections. Despite the global burden of influenza, there are currently no vaccine formulations approved for children less than 6 months of age. Given the challenges of conducting experimental studies involving pediatric patients, rhesus monkeys are an ideal laboratory animal model to investigate the maturation of pulmonary mucosal immune mechanisms during early life because they are most similar to humans with regard to postnatal maturation of lung structure and the immune system. Thus, our findings are highly relevant to translational medicine and these data may ultimately lead to novel approaches that enhance airway immunity in the very young.


• Characterization of The Nucleocytoplasmic Shuttle of The Matrix Protein of Influenza B Virus.
  Cao S, Jiang J, Li J, et al. Characterization of The Nucleocytoplasmic Shuttle of The Matrix Protein of Influenza B Virus. [JOURNAL ARTICLE]J Virol 2014 Apr 16.Influenza B virus is an enveloped negative-strand RNA virus, that contributes considerably to annual influenza illnesses in human. The matrix protein of influenza B virus (BM1) acts as a cytoplasmic-nuclear shuttling protein during the early and late stages of infection. The mechanism of this intracellular transport of BM1 was revealed through the identification of two leucine-rich CRM1-dependent nuclear export signals (NESs) (3-14aa and 124-133aa), one bipartite nuclear localization signal (NLS) (76-94aa), and two phosphorylation sites (80T and 84S) in BM1. The biological function of the NLS and NES regions were determined through the observation of the intracellular distribution of EGFP-tagged signal peptides, and WT, NES-mutant and NLS-mutant EGFP-BM1. Furthermore, the NLS phosphorylation sites 80T and 84S, were found to be required for the nuclear accumulation of EGFP-NLS and for the efficient binding of EGFP-BM1 to human importin-α 1. Moreover, all of these regions/sites were required for the generation of viable influenza B virus in a 12-plasmid virus rescue system.This study expands our understanding of the life cycle of influenza B virus by defining defines/presents the dynamic mechanism of the nucleocytoplasmic shuttle of BM1, and could provide a scientific basis for the development of anti-viral medication.


• Intra-host dynamics of influenza virus reassortment.
  Tao H, Steel J, Lowen AC Intra-host dynamics of influenza virus reassortment. [JOURNAL ARTICLE]J Virol 2014 Apr 16.The segmented nature of the influenza virus genome allows reassortment between co-infecting viruses. This process of genetic exchange vastly increases the diversity of circulating influenza viruses. The importance of reassortment to public health is clear from its role in the emergence of a number of epidemiologically important viruses, including novel pandemic and epidemic strains. To gauge its impact on within-host genomic variation, we tracked reassortment in co-infected guinea pigs over time and given matched or discordant doses of co-infecting viruses. To ensure unbiased detection of reassortants, we used parental viruses of equivalent fitness that differ only by non-coding nucleotide changes. These viruses were based on the isolate A/Panama/2007/1999 (H3N2). At a dose of 2×10(2) PFU, one parental virus was absent from each guinea pig throughout the time course, indicating the presence of a bottleneck. With an intermediate dose of 2×10(3) PFU, genomic diversity present in nasal lavage samples increased from 1-3 days post-infection (d.p.i.) and then declined by 6 d.p.i. With a high dose of 2×10(6) PFU, however, reassortment levels were high (avg. 59%) at 1 d.p.i. and remained stable. Even late in the course of infection, parental viruses were not eclipsed by reassortants, suggesting that a uniformly high multiplicity of infection was not achieved in vivo. Inoculation with approximately 10-fold discordant doses did not reduce reassortment relative to equivalent inputs, but markedly changed the spectrum of genotypes produced. Our data reveal the potential for reassortment to contribute to intra-host diversity in mixed influenza virus infection.Influenza virus reassortment is prevalent in nature and is a major contributor to the diversity of influenza viruses circulating in avian, swine, human and other host species. This diversity, in turn, increases the potential for influenza viruses to evade selective pressures or adapt to new host environments. As examples, reassortment was key to the emergence of the 1957, 1968 and 2009 pandemics; the unusually severe influenza epidemics of 2003, 1951 and 1947; and the rise in adamantane resistance among currently circulating human H3N2 viruses. Herein we reveal the diversity of viral genotypes generated over time in a host co-infected with two influenza viruses. We find that intra-host diversity driven by reassortment is dynamic and dependent on the amount of each virus initiating infection. Our results demonstrate the readiness with which reassortant influenza viruses arise, offering new insight into this important mechanism of influenza virus evolution.


• Phosphorylation of highly conserved serine residues in the influenza A virus nuclear export protein NEP plays a minor role in viral growth in human cells and mice.
  Reuther P, Giese S, Götz V, et al. Phosphorylation of highly conserved serine residues in the influenza A virus nuclear export protein NEP plays a minor role in viral growth in human cells and mice. [JOURNAL ARTICLE]J Virol 2014 Apr 16.Phosphorylation at the highly conserved serine residues S23 to S25 in NEP of influenza A viruses was suspected to regulate its nuclear export activity or polymerase-activity enhancing function. Mutation of these phosphoacceptor sites to either alanine or aspartic acid showed only a minor effect on both activities, but revealed the presence of other phosphoacceptor sites that might be involved in regulating NEP activity.


• Correction: identification and chronological analysis of genomic signatures in influenza a viruses.
   Correction: identification and chronological analysis of genomic signatures in influenza a viruses. [Journal Article]PLoS One 2014; 9(4):e95902.[This corrects the article DOI: 10.1371/journal.pone.0084638.].


• A marginal benefit approach for vaccinating influenza "superspreaders".
  Skene KJ, Paltiel AD, Shim E, et al. A marginal benefit approach for vaccinating influenza "superspreaders". [Journal Article]Med Decis Making 2014 May; 34(4):536-49.There is widespread recognition that interventions targeting "superspreaders" are more effective at containing epidemics than strategies aimed at the broaderHowever, little attention has been devoted to determining optimal levels of coverage for targeted vaccination strategies, given the nonlinear relationship between program scale and the costs and benefits of identifying and successfully administering vaccination to potential superspreaders.We developed a framework for such an assessment derived from a transmission model of seasonal influenza parameterized to emulate typical seasonal influenza epidemics in the US. We used this framework to estimate how the marginal benefit of expanded targeted vaccination changes with the proportion of the target population already vaccinated.The benefit of targeting additional superspreaders varies considerably as a function of both the baseline vaccination coverage and proximity to the herd immunity threshold. The general form of the marginal benefit function starts low, particularly for severe epidemics, increases monotonically until its peak at the point of herd immunity, and then plummets rapidly. We present a simplified transmission model, primarily designed to convey qualitative insight rather than quantitative precision. With appropriate contact data, future work could address more complex population structures, such as age structure and assortative mixing patterns. Our illustrative example highlights the general economic and epidemiological findings of our method but does not address intervention design, policy, and resource allocation issues related to practical implementation of this particular scenario.Our approach offers a means of estimating willingness to pay for search costs associated with targeted vaccination of superspreaders, which can inform policies regarding whether a targeted intervention should be implemented and, if so, up to what levels.


• Deletion of the Complement C5a Receptor Alleviates the Severity of Acute Pneumococcal Otitis Media following Influenza A Virus Infection in Mice.
  Tong HH, Lambert G, Li YX, et al. Deletion of the Complement C5a Receptor Alleviates the Severity of Acute Pneumococcal Otitis Media following Influenza A Virus Infection in Mice. [Journal Article]PLoS One 2014; 9(4):e95160.There is considerable evidence that influenza A virus (IAV) promotes adherence, colonization, and superinfection by S. pneumoniae (Spn) and contributes to the pathogenesis of otitis media (OM). The complement system is a critical innate immune defense against both pathogens. To assess the role of the complement system in the host defense and the pathogenesis of acute pneumococcal OM following IAV infection, we employed a well-established transtympanically-induced mouse model of acute pneumococcal OM. We found that antecedent IAV infection enhanced the severity of acute pneumococcal OM. Mice deficient in complement C1qa (C1qa-/-) or factor B (Bf -/-) exhibited delayed viral and bacterial clearance from the middle ear and developed significant mucosal damage in the eustachian tube and middle ear. This indicates that both the classical and alternative complement pathways are critical for the oto-immune defense against acute pneumococcal OM following influenza infection. We also found that Spn increased complement activation following IAV infection. This was characterized by sustained increased levels of anaphylatoxins C3a and C5a in serum and middle ear lavage samples. In contrast, mice deficient in the complement C5a receptor (C5aR) demonstrated enhanced bacterial clearance and reduced severity of OM. Our data support the concept that C5a-C5aR interactions play a significant role in the pathogenesis of acute pneumococcal OM following IAV infection. It is possible that targeting the C5a-C5aR axis might prove useful in attenuating acute pneumococcal OM in patients with influenza infection.