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Phosphatidylglycerol Suppresses Influenza A Virus Infection.Influenza A virus (IAV) is a worldwide public health problem causing 500,000 deaths each year. Palmitoyl-oleoyl-phophatidylglycerol (POPG) is a minor component of pulmonary surfactant, which has recently been reported to exert potent regulatory functions upon the innate immune system. In this report we demonstrate that POPG acts as a strong anti-viral agent against IAV. POPG markedly attenuated IL-8 production and cell death induced by IAV in cultured human bronchial epithelial cells. The lip ...201122052877
Intranasal administration of a flagellin-adjuvanted inactivated influenza vaccine enhances mucosal immune responses to protect mice against lethal infection.The influenza virus, a mucosal pathogen that infects the respiratory tract, is a major global health issue. There have been attempts to mucosally administer inactivated influenza vaccines to induce both mucosal and systemic immune responses. However, mucosally administered inactivated influenza vaccine has low immunogenicity, which is partially due to the lack of an effective mucosal adjuvant. The development of a safe and effective mucosal adjuvant is a prerequisite to the practical use of a mu ...201222051136
dual infection of novel influenza viruses a/h1n1 and a/h3n2 in a cluster of cambodian patients.during the early months of 2009, a novel influenza a/h1n1 virus (ph1n1) emerged in mexico and quickly spread across the globe. in october 2009, a 23-year-old male residing in central cambodia was diagnosed with ph1n1. subsequently, a cluster of four influenza-like illness cases developed involving three children who resided in his home and the children's school teacher. base composition analysis of internal genes using reverse transcriptase polymerase chain reaction and electrospray ionization m ...201122049058
[Study on the mutations within the whole genome of influenza virus subtype A/H3N2 strains circulated in Zhejiang province from 1998 to 2009].To analyze the consistency of evolution condition between HA gene and the whole genome of influenza virus subtype A/H3N2 strains isolated in Zhejiang province from 1998 to 2009, and to study the potential antigenic region on the whole genome.201122041565
Patterns of predicted T-cell epitopes associated with antigenic drift in influenza H3N2 hemagglutinin.Antigenic drift allowing escape from neutralizing antibodies is an important feature of transmission and survival of influenza viruses in host populations. Antigenic drift has been studied in particular detail for influenza A H3N2 and well defined antigenic clusters of this virus documented. We examine how host immunogenetics contributes to determination of the antibody spectrum, and hence the immune pressure bringing about antigenic drift. Using uTOPE™ bioinformatics analysis of predicted MHC b ...201122039539
prevalence of antibodies against seasonal influenza a and b viruses during the 2009-2010 and 2010-2011 influenza seasons in residents of pittsburgh, pa, usa.seroprevalence of antibodies against influenza viruses from 1000 people between the ages of 0 to 90 years of age (100 samples for each decade of life) in the pittsburgh, pa, usa was measured. one year removed from the outbreak of novel h1n1 influenza into the human population in the northern hemisphere and following the emergence of a new h3n2 influenza isolate, sera was collected to determine the hemagglutination-inhibition antibodies against influenza a/h1n1, a/h3n2, and b viruses representati ...201122037352
inefficient splicing of segment 7 and 8 mrnas is an inherent property of influenza virus a/brevig mission/1918/1 (h1n1) that causes elevated expression of ns1 protein.influenza a virus encodes two segments (7 and 8) that produce mrnas that can be spliced. we have investigated if naturally occurring sequence polymorphisms in the influenza a virus family affects splicing of these viral mrnas, as that could potentially alter the ns1/ns2- and/or m1/m2-protein ratios. we compared splicing efficiency of segment 7 and 8 mrnas of a/brevig mission/1918/1 (h1n1) and a/netherlands/178/95 (h3n2), as well as various h5n1 avian strains. results revealed that both segment 7 ...201222036312
molecular and antigenic evolution of human influenza a/h3n2 viruses in quebec, canada, 2009-2011.a/h3n2 variability leads to poor vaccine effectiveness when the vaccine strain is not well matched to the circulating virus.201222036039
Antiviral activity of arbidol, a broad-spectrum drug for use against respiratory viruses, varies according to test conditions.The therapeutic activity of arbidol was investigated against representatives of seven different virus families. Its 50% median effective concentration (EC(50) ) was 0.22-11.8?µg/ml (0.41-22?nM). Therapeutic indices of 91 were obtained for type 1 poliovirus and 1.9-8.5 for influenza A and B, human paramyxo-3, avian infectious bronchitis-, and Marek's disease viruses. Arbidol was more inhibitory for influenza A/Aichi/2/68 (H3N2) virus than rimantadine or amantadine (EC(50) 10 vs. >15 and >31.6?µg/ ...201222028179
emergence of a new swine h3n2 and pandemic (h1n1) 2009 influenza a virus reassortant in two canadian animal populations, mink and swine.a swine h3n2 (swh3n2) and pandemic (h1n1) 2009 (ph1n1) influenza a virus reassortant (swh3n2/ph1n1) was detected in canadian swine at the end of 2010. simultaneously, a similar virus was also detected in canadian mink based on partial viral genome sequencing. the origin of the new swh3n2/ph1n1 viral genes was related to the north american swh3n2 triple-reassortant cluster iv (for hemagglutinin [ha] and neuraminidase [na] genes) and to ph1n1 for all the other genes (m, np, ns, pb1, pb2, and pa). ...201122012020
respiratory syncytial virus (rsv) community-acquired pneumonia (cap) in a hospitalized adult with human immunodeficiency virus (hiv) mimicking influenza a and pneumocystis (carinii) jiroveci pneumonia (pcp).respiratory syncytial virus (rsv) is an important cause of lower respiratory tract infections in young children, the elderly, and immunocompromised hosts, but rsv is a rare cause of community-acquired pneumonia (cap) in hospitalized adults with human immunodeficiency virus (hiv). in patients with hiv, cap is most frequently attributable to the usual bacterial respiratory pathogens that cause cap in immunocompetent hosts, eg, streptococcuspneumoniae or hemophilus influenzae. adults with hiv are a ...201222005289
genetic characterization of h1n2 influenza a virus isolated from sick pigs in southern china in 2010.in china h3n2 and h1n1 swine influenza viruses have been circulating for many years. in january 2010, before swine were infected with foot and mouth disease in guangdong, some pigs have shown flu-like symptoms: cough, sneeze, runny nose and fever. we collected the nasopharyngeal swab of all sick pigs as much as possible. one subtype h1n2 influenza viruses were isolated from the pig population. the complete genome of one isolate, designated a/swine/guangdong/1/2010(h1n2), was sequenced and compar ...201121995516
neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective.neuraminidase inhibitors (nais) are vital in managing seasonal and pandemic influenza infections. nai susceptibilities of virus isolates (n = 5540) collected during the 2008-2009 influenza season were assessed in the chemiluminescent neuraminidase inhibition (ni) assay. box-and-whisker plot analyses of log-transformed ic(50)s were performed for each virus type/subtype and nai to identify outliers which were characterized based on a statistical cutoff of ic(50) >3 interquartile ranges (iqr) from ...201021994620
Clinical and socioeconomic impact of different types and subtypes of seasonal influenza viruses in children during influenza seasons 2007/2008 and 2008/2009.There are few and debated data regarding possible differences in the clinical presentations of influenza A/H1N1, A/H3N2 and B viruses in children. This study evaluates the clinical presentation and socio-economic impact of laboratory-confirmed influenza A/H1N1, A/H3N2 or B infection in children attending an Emergency Room because of influenza-like illness.201121992699
genetic evolution of low pathogenecity h9n2 avian influenza viruses in tunisia: acquisition of new mutations.since the end of 2009, h9n2 has emerged in tunisia causing several epidemics in poultry industry resulting in major economic losses. to monitor variations of influenza viruses during the outbreaks, tunisian h9n2 virus isolates were identified and genetically characterized.201121992186
FluReF, an automated flu virus reassortment finder based on phylogenetic trees.Reassortments are events in the evolution of the genome of influenza (flu), whereby segments of the genome are exchanged between different strains. As reassortments have been implicated in major human pandemics of the last century, their identification has become a health priority. While such identification can be done "by hand" on a small dataset, researchers and health authorities are building up enormous databases of genomic sequences for every flu strain, so that it is imperative to develop ...201121989112
Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice.A mouse model was used to determine if protective immunity to influenza A virus infection differs between the sexes. The median lethal dose of H1N1 or H3N2 was lower for naïve females than males. After a sublethal, primary infection with H1N1 or H3N2, females and males showed a similar transient morbidity, but females generated more neutralizing and total anti-influenza A virus antibodies. Immunized males and females showed similar protection against secondary challenge with a homologous virus, ...201121983155
Dose-Response Assessment for Influenza A Virus Based on Data Sets of Infection with its Live Attenuated Reassortants.Reported data sets on infection of volunteers challenged with wild-type influenza A virus at graded doses are few. Alternatively, we aimed at developing a dose-response assessment for this virus based on the data sets for its live attenuated reassortants. Eleven data sets for live attenuated reassortants that were fit to beta-Poisson and exponential dose-response models. Dose-response relationships for those reassortants were characterized by pooling analysis of the data sets with respect to vir ...201121977924
Revisiting the 1976 "swine flu" vaccine clinical trials: cross-reactive hemagglutinin and neuraminidase antibodies and their role in protection against the 2009 H1N1 pandemic virus in mice.The 2009 H1N1 pandemic viruses are genetically similar to A/New Jersey/76 H1N1 virus (NJ/76), the strain selected for the 1976 "swine flu" vaccines. Approximately 45 million people in the United States were vaccinated against NJ/76 30 years ago, but the impact of this nationwide immunization on the current pandemic is largely unknown.201121976461
A plant-based system for rapid production of influenza vaccine antigens.Please cite this paper as: Shoji et al. (2011) A plant-based system for rapid production of influenza vaccine antigens. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00295.x. Background Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is t ...201121974811
Laninamivir octanoate: a new long-acting neuraminidase inhibitor for the treatment of influenza.Oseltamivir and zanamivir are well-established and well-researched drugs for the treatment of influenza in Japan and the rest of the world. A new neuraminidase inhibitor, laninamivir octanoate, has been approved for use in Japanese clinics. Laninamivir octanoate is an inhaled drug with unique characteristics. The inhaled laninamivir octanoate is converted into its active form, laninamivir, in the lungs where a high concentration persists for a long period of time. The concentration of laninamivi ...201121973296
interaction of porcine conventional dendritic cells with swine influenza virus.swine influenza virus (swiv) causes sub-acute or acute respiratory infections on swine farms and pigs can act as "mixing vessels" for new influenza strains. knowledge of the immune response of swiv in its natural host, pigs, is very limited. dendritic cells (dcs) mediate the induction of immunity to pathogens, but their interaction with swiv has not been fully characterized. thus, porcine bone marrow derived dcs (pobmdcs) were exposed to a circulating strain of h3n2 swiv in vitro. infection of p ...201121962444
Pandemic and seasonal human influenza virus infections in domestic cats: prevalence, association with respiratory disease, and seasonality patterns.Domestic cats have several features that make them ideal vehicles for interspecies transmission of influenza viruses; however, they have been largely overlooked as potential reservoirs or bridging hosts. In this study, we conducted serological surveillance to assess the prevalence of novel pandemic H1N1 as well as seasonal human influenza virus infections in domestic cats in Ohio. Four hundred serum samples collected from domestic cats (September 2009 to September 2010) were tested using a hemag ...201121956989
Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety.Please cite this paper as: Tavana et al. (2011) Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00290.x. Background Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to var ...201121955954
genetic relationship of h3 subtype avian influenza viruses isolated from domestic ducks and wild birds in korea and their pathogenic potential in chickens and ducks.the h3 subtype avian influenza virus (aiv) is one of the most frequently isolated subtypes in domestic ducks, live poultry markets, and wild birds in korea. in 2002-2009, a total of 45 h3 subtype aivs were isolated from the feces of clinically normal domestic ducks (n=28) and wild birds (n=17). the most prevalent subtypes in domestic ducks were h3n2 (35.7%), h3n6 (35.7%), h3n8 (25.0%), and h3n1 (3.6%, novel subtype in domestic duck in korea). in contrast, h3n8 (70.6%) is the most prevalent subty ...201121955449
multisite virological influenza surveillance in india: 2004-2008.please cite this paper as: chadha et al. (2011) multi site virological influenza surveillance in india: 2004-2008. influenza and other respiratory viruses doi: 10.1111/j.1750-2659.2011.00293.x. background  influenza surveillance is important to identify circulating, emerging/reemerging strains and unusual epidemiological trends. with these objectives, a multisite human influenza surveillance network was initiated in india in 2004. methods  epidemiologic data and throat swabs for laboratory testi ...201121955356
in vitro generation of influenza-specific polyfunctional cd4(+) t cells suitable for adoptive immunotherapy.abstract background aims. influenza viruses cause potentially fatal respiratory infections in stem cell transplant patients. specific t cells provide long-lived host adaptive immunity to influenza viruses, and the potential for generating such cells for clinical use was investigated. methods. the inactivated influenza vaccine (fluvax) approved for human use was used as the antigen source. monocyte-derived dendritic cells pulsed with fluvax were used to stimulate autologous peripheral blood mon ...201121954837
cross-protective peptide vaccine against influenza a viruses developed in hla-a*2402 human immunity model.the virus-specific cytotoxic t lymphocyte (ctl) induction is an important target for the development of a broadly protective human influenza vaccine, since most ctl epitopes are found on internal viral proteins and relatively conserved. in this study, the possibility of developing a strain/subtype-independent human influenza vaccine was explored by taking a bioinformatics approach to establish an immunogenic hla-a24 restricted ctl epitope screening system in hla-transgenic mice.201121949735
transmission of aerosolized seasonal h1n1 influenza a to ferrets.influenza virus is a major cause of morbidity and mortality worldwide, yet little quantitative understanding of transmission is available to guide evidence-based public health practice. recent studies of influenza non-contact transmission between ferrets and guinea pigs have provided insights into the relative transmission efficiencies of pandemic and seasonal strains, but the infecting dose and subsequent contagion has not been quantified for most strains. in order to measure the aerosol infect ...201121949718
safety and immunogenicity of live attenuated and inactivated influenza vaccines in children with cancer.the safety and immunogenicity of live, attenuated influenza vaccine (laiv) has not been compared to that of the standard trivalent inactivated vaccine (tiv) in children with cancer.201121949042
History of Swine Influenza Viruses in Asia.The pig is one of the main hosts of influenza A viruses and plays important roles in shaping the current influenza ecology. The occurrence of the 2009 H1N1 pandemic influenza virus demonstrated that pigs could independently facilitate the genesis of a pandemic influenza strain. Genetic analyses revealed that this virus was derived by reassortment between at least two parent swine influenza viruses (SIV), from the northern American triple reassortant H1N2 (TR) and European avian-like H1N1 (EA) li ...201121948002
A practical synthesis of zanamivir phosphonate congeners with potent anti-influenza activity.Two phosphonate compounds 1a (4-amino-1-phosphono-DANA) and 1b (phosphono-zanamivir) are synthesized and shown more potent than zanamivir against the neuraminidases of avian and human influenza viruses, including the oseltamivir-resistant strains. For the first time, the practical synthesis of these phosphonate compounds is realized by conversion of sialic acid to peracetylated phosphono-DANA diethyl ester (5) as a key intermediate in three steps by a novel approach. In comparison with zanamivir ...201121942552
Antigenic variability in Neuraminidase protein of Influenza A/H3N2 vaccine strains (1968 - 2009).Antigenic drift and shift involving the surface proteins of Influenza virus gave rise to new strains that caused epidemics affecting millions of people worldwide over the last hundred years. Variations in the membrane proteins like Hemagglutinin (HA) and Neuraminidase (NA) necessitates new vaccine strains to be updated frequently and poses challenge to effective vaccine design. Though the HA protein, the primary target of the human immune system, has been well studied, reports on the antigenic v ...201121938209
immunopathogenic and antibacterial effects of h3n2 influenza a virus pb1-f2 map to amino acid residues 62, 75, 79, and 82.the influenza a virus protein pb1-f2 has been linked to the pathogenesis of both primary viral and secondary bacterial infections. h3n2 viruses have historically expressed full-length pb1-f2 proteins with either proinflammatory (e.g., from influenza a/hong kong/1/1968 virus) or noninflammatory (e.g., from influenza a/wuhan/359/1995 virus) properties. using synthetic peptides derived from the active c-terminal portion of the pb1-f2 protein from those two viruses, we mapped the proinflammatory dom ...201121937639
Assessment of the antiviral properties of recombinant porcine SP-D against various influenza A viruses in vitro.The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral ...201121935489
Genetic structure of human A/H1N1 and A/H3N2 influenza virus on Corsica Island: phylogenetic analysis and vaccine strain match, 2006-2010.The aim of this study was to analyse the genetic patterns of Hemagglutinin (HA) genes of influenza A strains circulating on Corsica Island during the 2006-2009 epidemic seasons and the 2009-2010 pandemic season.201121935413
receptor tyrosine kinase inhibitors that block replication of influenza a and other viruses.we have previously reported that two receptor tyrosine kinase inhibitors (rtkis), called ag879 and tyrphostin a9 (a9), can each block the replication of influenza a virus in cultured cells. in this study, we further characterized the in vitro antiviral efficacies and specificities of these agents. the 50% effective concentration (ec(50)) of each against influenza a was found to be in the high nanomolar range, and the selectivity index (si = 50% cytotoxic concentration [cc(50)]/ec(50)) was determ ...201121930873
In vitro and in vivo efficacy of fluorodeoxycytidine analogs against highly pathogenic avian influenza H5N1, seasonal, and pandemic H1N1 virus infections.Various fluorodeoxyribonucleosides were evaluated for their antiviral activities against influenza virus infections in vitro and in vivo. Among the most potent inhibitors was 2'-deoxy-2'-fluorocytidine (2'-FdC). It inhibited various strains of low and highly pathogenic avian influenza H5N1 viruses, pandemic H1N1 viruses, an oseltamivir-resistant pandemic H1N1 virus, and seasonal influenza viruses (H3N2, H1N1, influenza B) in MDCK cells, with the 90% inhibitory concentrations ranging from 0.13 to ...201121925541
Burden of the 1999-2008 seasonal influenza epidemics in Italy: comparison with the H1N1v (A/California/07/09) pandemic.Despite preventive efforts, seasonal influenza epidemics are responsible for substantial morbidity and mortality every year worldwide, including developed countries. The A/H1N1v pandemic imposed a considerable healthcare and economic burden. In order to obtain an accurate estimate of the economic burden of influenza, and hence to guide policymakers effectively, systematic studies are necessary. To this end, data from epidemiological surveillance are essential. To estimate the impact of the 1999- ...201121922688
Host genetic background and the innate inflammatory response of lung to influenza virus.Many studies of influenza severity have focused on viral properties that confer virulence, whereas the contributory role of the host genetic background on infection severity remains largely unexplored. In this study, we measure the impact of inoculation with influenza virus in four strains of inbred mice - BALB/cByJ, C57BL/6J, A/J, and DBA/2J. To evaluate the extent to which responses are inherent to lung per se, as opposed to effects of the systemic response to lung infection, we also measured ...201221920449
the dba.2 mouse is susceptible to disease following infection with a broad, but limited, range of influenza a and b viruses.we assessed the relative susceptibilities to disease of the dba.2 and c57bl/6 mouse models upon infection with a range of influenza a and b viruses. dba.2 mice were more susceptible to disease upon inoculation with human h1n1 influenza a virus strains, several swine influenza viruses, and influenza b viruses but were not overtly susceptible to infection with human seasonal h3n2 strains. hemagglutination inhibition and immunoglobulin isotype profiling indicated that dba.2 and c57bl/6 mice generat ...201121917963
anticipating the species jump: surveillance for emerging viral threats.zoonotic disease surveillance is typically triggered after animal pathogens have already infected humans. are there ways to identify high-risk viruses before they emerge in humans? if so, then how and where can identifications be made and by what methods? these were the fundamental questions driving a workshop to examine the future of predictive surveillance for viruses that might jump from animals to infect humans. virologists, ecologists and computational biologists from academia, federal gove ...201121914152
development of diva (differentiation of infected from vaccinated animals) vaccines utilizing heterologous na and ns1 protein strategies for the control of triple reassortant h3n2 influenza in turkeys.since 2003, triple reassortant (tr) swine h3n2 influenza viruses containing gene segments from human, avian, and swine origins have been detected in the u.s. turkey populations. the initial outbreak that occurred involved birds that were vaccinated with the currently available h3 swine- and avian-origin influenza vaccines. antigenically, all turkey swine-lineage tr h3n2 isolates are closely related to each other but show little or no antigenic cross-reactivity with the avian origin or swine orig ...201121907751
avian glycan-specific igm monoclonal antibodies for the detection and quantitation of type a and b haemagglutinins in egg-derived influenza vaccines.two igm monoclonal antibodies (mabs), y6f5 and y13f9, were selected during a screening of clones obtained immunising balb/c mice with purified envelop proteins of the a/sydney/5/97 (h3n2) ivr108 influenza strain. these mabs recognised avian glycans on the haemagglutinin (ha) of the virus. this broad recognition allowed these mabs to be used as enzyme-labelled secondary antibody reagents in a strain specific enzyme-linked immunosorbent assay (elisa) in combination with a capture mab that recognis ...201121907241
temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. the host response is an important determinant of disease progression. in order to delineate host molecular responses that differentiate symptomatic and asymptomatic influenza a infection, we inoculated 17 healthy adults with live influenza (h3n2/wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. here we present distinct tra ...201121901105
swine-origin influenza a (h3n2) virus infection in two children--indiana and pennsylvania, july-august 2011.influenza a viruses are endemic in many animal species, including humans, swine, and wild birds, and sporadic cases of transmission of influenza a viruses between humans and animals do occur, including human infections with avian-origin influenza a viruses (i.e., h5n1 and h7n7) and swine-origin influenza a viruses (i.e., h1n1, h1n2, and h3n2). genetic analysis can distinguish animal origin influenza viruses from the seasonal human influenza viruses that circulate widely and cause annual epidemic ...201121900876
[High-yield reassortant virus containing hemagglutinin and neuraminidase genes of pandemic influenza A/Moscowl/01/2009 (H1N1) virus].The crossing of influenza A/Moscow/01/2009 (H1N1) virus and reassortant strain X31 (H3N2) containing the genes of internal and non-structural proteins of A/Puerto Rico/8/34 (H1N1) strain gave rise to reassortant virus ReM8. The reassortant contained hemagglutinin (HA) and neuraminidase (NA) genes of pandemic 2009 influenza virus and 6 genes of high-yield A/Puerto Rico/8/34 (H1N1) strain. The reassortant ReM8 produced higher yields in the embryonated chicken eggs than the parent pandemic virus, a ...201121899062
evolutionary pathways of the pandemic influenza a (h1n1) 2009 in the uk.the emergence of the influenza (h1n1) 2009 virus provided a unique opportunity to study the evolution of a pandemic virus following its introduction into the human population. virological and clinical surveillance in the uk were comprehensive during the first and second waves of the pandemic in 2009, with extensive laboratory confirmation of infection allowing a detailed sampling of representative circulating viruses. we sequenced the complete coding region of the haemagglutinin (ha) segment of ...201121887318
Rapid detection and subtyping of human influenza A viruses and reassortants by pyrosequencing.Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance.201121886790
Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays.Please cite this paper as: Cwach et al. (2011) Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00283.x. Background Prior to detection of an antibody response toward influenza viruses using the hemagglutination inhibition assay (HAI), sera are routinely treated to inactivate innate inhibitors using both heat inactivation (56°C) and recombinant neuraminidase [receptor-des ...201121883963
the m segment of the 2009 new pandemic h1n1 influenza virus is critical for its high transmission efficiency in the guinea pig model.a remarkable feature of the 2009 pandemic h1n1 influenza virus is its efficient transmissibility in humans compared to that of precursor strains from the triple-reassortant swine influenza virus lineage, which cause only sporadic infections in humans. the viral components essential for this phenotype have not been fully elucidated. in this study, we aimed to determine the viral factors critical for aerosol transmission of the 2009 pandemic virus. single or multiple segment reassortments were mad ...201121880744
Differential pulmonary transcriptomic profiles in murine lungs infected with low and highly virulent influenza H3N2 viruses reveal dysregulation of TREM1 signaling, cytokines, and chemokines.Investigating the relationships between critical influenza viral mutations contributing to increased virulence and host expression factors will shed light on the process of severe pathogenesis from the systems biology perspective. We previously generated a mouse-adapted, highly virulent influenza (HVI) virus through serial lung-to-lung passaging of a human influenza H3N2 virus strain that causes low virulent influenza (LVI) in murine lungs. This HVI virus is characterized by enhanced replication ...201121874528
naturally occurring antibodies in humans can neutralize a variety of influenza virus strains, including h3, h1, h2, and h5.influenza a viruses are classified into 16 subtypes according to the serotypes of hemagglutinin (ha). it is generally thought that neutralizing antibodies (abs) are not broadly cross-reactive among ha subtypes. we examined the repertoire of neutralizing abs against influenza viruses in humans. b lymphocytes were collected from donors by apheresis, and ab libraries were constructed by using phage-display technology. anti-ha clones were isolated by screening with h3n2 viruses. their binding activi ...201121865387
[the 50% effective dose (ed50a) of seasonal spilt influenza vaccine in mice].to evaluate the seasonal influenza spilt vaccine's immunogenicity and the 50% effective dose (ed50a) of hemagglutin (ha) that can make 50% of the mice hemagglutination inhibition antibody (hi) titers to 40.201121863626
Live attenuated influenza vaccine (FluMist®; Fluenz™): a review of its use in the prevention of seasonal influenza in children and adults.Live attenuated influenza vaccine (LAIV) is an intranasally administered trivalent, seasonal influenza vaccine that contains three live influenza viruses (two type A [H1N1 and H3N2 subtypes] and one type B). LAIV was effective in protecting against culture-confirmed influenza caused by antigenically matched and/or distinct viral strains in children aged =71 months enrolled in three phase III trials. LAIV was superior to trivalent inactivated influenza vaccine (TIV) in protecting against influenz ...201121861544
anti-influenza virus activity of tricin, 4',5,7-trihydroxy-3',5'-dimethoxyflavone.we examined the anti-influenza virus activity of tricin, 4',5,7-trihydroxy-3',5'-dimethoxyflavone, against five viruses: a/solomon islands/3/2006 (h1n1), a/hiroshima/52/2005 (h3n2), a/california/07/2009 (h1n1pdm), a/narita/1/2009 (h1n1pdm) and b/malaysia/2506/2004 strains in vitro and against a/pr/8/34 virus in vivo.201121860068
pandemic novel 2009 h1n1 influenza: what have we learned?in march 2009, cases of influenza-like illness in mexico caused by a novel h1n1 virus containing genes from swine, avian, and human influenza strains were reported. within several weeks, 2009 h1n1 disseminated rapidly and was the predominant influenza strain globally. on june 11, 2009, the world health organization declared that criteria for an influenza pandemic had been met. concern that this pandemic would rival the 1918 pandemic was high. fortunately, that was not the case. influenza-related ...201121858744
immunogenicity and safety of intradermal influenza vaccine in children.in order to compare the immunogenicity and safety of different doses of trivalent influenza vaccine (tiv) administered intradermallly (id) with those evoked by a full dose of intramuscular (im) virosomal-adjuvanted influenza vaccine (va-tiv), 112 previously primed healthy children aged ≥ 3 years were randomised to receive 9 μg or 15 μg of each strain of id-tiv, or a full im dose (15 μg of each strain) of va-tiv. the a/h1n1 and a/h3n2 seroconversion and seroprotection rates were ≥ 90% and geometr ...201121855592
novel antiviral activity of neuraminidase inhibitors against an avian influenza a virus.abstract:201121851647
Outbreak of swine influenza in Argentina reveals a non-contemporary human H3N2 virus highly transmissible among pigs.Sporadic outbreaks of human H3N2 influenza A virus (IAV) infections in swine populations have been reported in Asia, Europe and North America since 1970. In South America, serological surveys in pigs indicate that IAVs of the H3 and H1 subtypes are currently in circulation; however, neither virus isolation nor characterization has been reported. In November 2008, an outbreak of respiratory disease in pigs consistent with swine influenza virus (SIV) infection was detected in Argentina. The curren ...201121849519
impact of pandemic a/h1n1/2009 influenza on children and their families: comparison with seasonal a/h1n1 and a/h3n2 influenza viruses.objectives: to make a direct comparison between the total burden of pandemic influenza and that of other seasonal influenza a viral subtypes in otherwise healthy children. methods: the total clinical and socioeconomic burden of pandemic a/h1n1/2009 influenza was compared with that of seasonal influenza a viral subtypes in 389 otherwise healthy children with a/h1n1/2009, 126 with seasonal a/h1n1 and 486 with seasonal a/h3n2 infection referred to the emergency room and hospitalised in the in-patie ...201121839113
respiratory viruses involved in influenza-like illness in a greek pediatric population during the winter period of the years 2005-2008.viruses are the major cause of pediatric respiratory tract infection and yet many suspected cases of illness remain uncharacterized. this study aimed to determine the distribution of several respiratory viruses in children diagnosed as having influenza-like illness, over the winter period of 2005-2008. molecular assays including conventional and real time pcr protocols, were employed to screen respiratory specimens, collected by clinicians of the influenza sentinel system and of outpatient pedia ...201121837803
Study on phylogenetic relationships, variability, and correlated mutations in m2 proteins of influenza virus a.M2 channel, an influenza virus transmembrane protein, serves as an important target for antiviral drug design. There are still discordances concerning the role of some residues involved in proton transfer as well as the mechanism of inhibition by commercial drugs. The viral M2 proteins show high conservativity; about 3/4 of the positions are occupied by one residue in over 95%. Nine M2 proteins from the H3N2 strain and possibly two proteins from H2N2 strains make a phylogenic cluster closely rel ...201121829678
characterization of influenza a outbreaks in minnesota swine herds and measures taken to reduce the risk of zoonotic transmission.influenza a virus infections commonly cause respiratory disease in swine and can be transmitted between people and pigs, with potentially novel strains introduced into herds and spilling back into the human population. the goals of this study were to characterize influenza infections in minnesota pigs and assess biosecurity measures used by swine workers. veterinarians submitting influenza-positive swine samples to the university of minnesota veterinary diagnostic laboratory between october 2007 ...201121824375
serological and virological surveillance of swine h1n1 and h3n2 influenza virus infection in two farms located in hubei province, central china.swine influenza viruses h1n1 and h3n2 have been reported in the swine population worldwide. from june 2008 to june 2009, we carried out serological and virological surveillance of swine influenza in the hubei province in central china. the serological results indicated that antibodies to h1n1 swine influenza virus in the swine population were high with a 42.5% (204/480) positive rate, whereas antibodies to h3n2 swine influenza virus were low with a 7.9% (38/480) positive rate. virological survei ...201121824344
comparison of two real-time rt-pcr-based systems for the detection and typing of the pandemic influenza a virus, 2009.during the 2009 pandemic the virology laboratory of l. spallanzani, rome, italy, adopted a real-time rt-pcr developed by the centers for disease control and prevention (cdc), atlanta, georgia to diagnose pandemic influenza a/h1n1 (h1n1pdm). a new multiplex real-time rt-pcr distributed by astra diagnostics, coupled with the extraction system developed and commercialized by siemens healthcare diagnostics (referred to as the realstar system), was tested for the ability to detect and type influenza ...201121807027
viral genetic sequence variations in pandemic h1n1/2009 and seasonal h3n2 influenza viruses within an individual, a household and a community.background: there are few data in the literature on viral sequence variation between host generations/successive transmission events. relatively little is known about the sequence heterogeneity of the influenza viruses transmitted within families. objectives: to study the molecular epidemiology of influenza virus and to determine the sequence variation within an individual, a household and a community during the first wave of influenza pandemic in 2009. study design: a prospective study of house ...201121802983
seroprevalence and risk factors for swine influenza zoonotic transmission in swine workers from northwestern mexico.summary a cross-sectional study was conducted to evaluate the transmission of swine influenza through occupational exposure and to assess some risk factors for zoonotic transmission in workers from commercial farms in mexico. seroprevalence to swine influenza subtypes was determined by hemagglutinin inhibition assay and was higher in exposed (e), in comparison with unexposed (ue) participants (p < 0.05). percentages of seropositivity between ue and e were 28.57% and 19.35% to a/newcaledonia/20/9 ...201121801341
evolution of h3n2 influenza virus in a guinea pig model.studies of influenza virus evolution under controlled experimental conditions can provide a better understanding of the consequences of evolutionary processes with and without immunological pressure. characterization of evolved strains assists in the development of predictive algorithms for both the selection of subtypes represented in the seasonal influenza vaccine and the design of novel immune refocused vaccines. to obtain data on the evolution of influenza in a controlled setting, naïve and ...201121799726
prediction of probable mutations in influenza virus hemagglutinin protein based on large-scale ab initio fragment molecular orbital calculations.ab initio electronic-state calculations for influenza virus hemagglutinin (ha) trimer complexed with fab antibody were performed on the basis of the fragment molecular orbital (fmo) method at the second and third-order møller-plesset (mp2 and mp3) perturbation levels. for the protein complex containing 2351 residues and 36,160 atoms, the inter-fragment interaction energies (ifies) were evaluated to illustrate the effective interactions between all the pairs of amino acid residues. by analyzing t ...201121798776
synthesis, antiviral and cytotoxic investigation of 2-phenyl-3-substituted quinazolin-4(3h)-ones.a series of 3(benzylideneamino)-2-phenyl quinazoline-4(3h)-ones was synthesized by reaction of 3-amino-2-phenyl-3h-quinazoline-4-one with various carbonyl compounds.201121796872
critical role of serpinb1 in regulating inflammatory responses in pulmonary influenza infection.background. excessive inflammatory host response increases morbidity and mortality associated with seasonal respiratory influenza, and highly pathogenic virus strains are characterized by massive infiltration of monocytes and/or macrophages that produce a storm of injurious cytokines. methods. here, we examined the role in respiratory influenza of serpinb1, an endogenous inhibitor of the serine proteases elastase, cathepsin g, and proteinase-3, increasingly recognized as regulators of inflammati ...201121791661
[compare real-time rt-pcr with two culture methods for influenza virus detection].real-time rt-pcr, cell culture and embryonated eggs culture for influenza detection were compared by analyzing the data of influenza surveillance in shenzhen in second half of 2009.201121789860
strength and tempo of selection revealed in viral gene genealogies.abstract: background: rna viruses evolve extremely quickly, allowing them to rapidly adapt to new environmental conditions. viral pathogens, such as influenza virus, exploit this capacity for evolutionary change to persist within the human population despite substantial immune pressure. understanding the process of adaptation in these viral systems is essential to our efforts to combat infectious disease. results: through analysis of simulated populations and sequence data from influenza a (h3n2 ...201121787390
[restriction analysis of genome composition of live influenza vaccine].live attenuated cold-adapted influenza vaccine (liv) has been used in russia for over 50 years and proved to be safe and effective. currently, russian reassortant laiv is based on influenza aileningrad/134/17/57 (h2n2) and b/ussr/60/69 master donor viruses (mdvs) which are cold-adapted (ca), temperature-sensitive (ts), and attenuated (att), respectively. the mdvs are used to generate attenuated reassortant vaccine viruses containing the surface antigens of current wild type (wt) influenza a (hin ...201121786624
[monoclonal antibodies with high virus-neutralizing activity against pandemic influenza virus a/llv-moscow/01/2009 (h1n1)swl].the authors have obtained a panel of 7 monoclonal antibodies (mabs) against pandemic influenza virus a/iiv-moscow/01/2009 (hin1)swl isolated in russia. one mab is directed to a np protein linear epitope and interacts with all the influenza a viruses under study. six other mabs are directed to h1 hemagglutinin conformation-dependent determinants and detect homologous virus in the hemagglutination-inhibition test, enzyme immunoassay, immunofluorescence and virus neutralization tests. mabs differen ...201121786621
integrating silicon nanowire field effect transistor, microfluidics and air sampling techniques for real-time monitoring biological aerosols.numerous threats from biological aerosol exposures, such as those from h1n1 influenza, sars, bird flu, and bioterrorism activities necessitate the development of a real-time bioaerosol sensing system, which however is a long-standing challenge in the field. here, we developed a real-time monitoring system for airborne influenza h3n2 viruses by integrating electronically addressable silicon nanowire (sinw) sensor devices, microfluidics and bioaerosol-to-hydrosol air sampling techniques. when airb ...201121780777
a novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic h1n1 influenza viruses in mice.the ha protein of the 2009 pandemic h1n1 viruses (h1n1pdm) is antigenically closely related to the ha of classical north american swine h1n1 influenza viruses (ch1n1). since 1998, through mutation and reassortment of ha genes from human h3n2 and h1n1 influenza viruses, swine influenza strains are undergoing substantial antigenic drift and shift. in this report we describe the development of a novel monoclonal antibody (s-oiv-3b2) that shows high hemagglutination inhibition (hi) and neutralizatio ...201121774955
[immune protective effectiveness of seasonal influenza spilt vaccine against homologous and heterogonous subtypes of influenza virus in mice].to investigate the seasonal influenza split vaccine's immune protective effectiveness against the homologous and heterogonous subtypes of influenza a virus challenge and the relationship between the protective effectiveness and hemagglutination inhibition (hi) antibody titer in mice. two components of h1n1 and h3n2 in chinese 2008-2009 seasonal influenza spilt vaccine, were derived from vaccine strain a/brisbane/59/2007 (h1n1)-like virus and a/brisbane/10/2007 (h3n2)-like virus respectively, and ...201121774253
pandemic (h1n1) 2009 and hajj pilgrims who received predeparture vaccination, egypt.in egypt, vaccination against pandemic (h1n1) 2009 virus was required of pilgrims departing for the 2009 hajj. a survey of 551 pilgrims as they returned to egypt found 542 (98.1% [weighted]) reported receiving the vaccine; 6 (1.0% [weighted]) were infected with influenza virus a (h3n2) but none with pandemic (h1n1) 2009 virus.201121762583
discovery of dihydro-alkyloxy-benzyl-oxopyrimidines as promising anti-influenza virus agents.a series of novel dihydro-alkyloxy-benzyl-oxopyrimidine (dabo) derivatives were synthesized and evaluated for their activity against influenza virus in mdck cells. four dabo derivatives (4a1, 4a2, 4a3, and 4d1) showed potent activity against influenza virus. among them, compound 4a3 was the most promising lead with broad activity against influenza a (antiviral ec(50) values of 9 and 18 µm for the a/h1n1 and a/h3n2 subtype, respectively) and influenza b virus (ec(50) : 33 µm). the antiviral mecha ...201121752202
influenza a (h3n2) associated acute necrotising encephalopathy.we present a case of 16 year old female admitted with complaints of influenza like symptoms followed by convulsions and sudden impairment of consciousness. magnetic resonance imaging abnormalities were found in bilateral thalami including cerebellum. diagnosis of influenza associated acute necrotizing encephalopathy was made on the basis of clinical features, neuroimaging findings and isolation of influenza a(h3n2) virus from throat swab. this is probably first case of influenza associated acute ...201121751668
swine influenza virus a (h3n2) infection in human, kansas, usa, 2009.to the editor: triple-reassortant swine influenza viruses (sivs), which contain genes from human, swine, and avian influenza a viruses, have been enzootic among swine herds in the united states since the late 1990s (1). although uncommon, occasional transmission of triple-reassortant sivs from swine to humans has occurred (2-4). before april 2009, only limited, nonsustained human-to-human transmission of sivs had been reported (5-7). although an animal source for pandemic (h1n1) 2009 virus has y ...201121749798
serological survey of antibodies to influenza a viruses in a group of people without a history of influenza vaccination.clin microbiol infect abstract: a serological survey for antibodies to influenza viruses was performed in china on a group of people without a history of influenza vaccination. using the haemagglutination inhibition (hi) assay, we found seropositivity rates for seasonal h3n2 to be significantly higher than those for seasonal h1n1. samples positive for antibodies to the pandemic (h1n1) 2009 virus increased from 0.6% pre-outbreak to 4.5% (p <0.01) at 1 year post-outbreak. interestingly, hi and neu ...201121749549
measurement of enzymatic activity and specificity of human and avian influenza neuraminidases from whole virus by glycoarray and maldi-tof mass spectrometry.influenza neuraminidases hydrolyze the ketosidic linkage between n-acetylneuraminic acid and its adjacent galactose residue in sialosides. this enzyme is a tetrameric protein that plays a critical role in the release of progeny virions. several methods have been described for the determination of neuraminidase activity, usually based on colorimetric, fluorescent, or chemiluminescent detection. however, only a few of these tests allow discrimination of the sialyl-linkage specificity (i.e., α2-3- ...201121739555
comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-pcr assays.many acute respiratory illness surveillance systems collect and test nasopharyngeal (np) and/or oropharyngeal (op) swab specimens, yet there are few studies assessing the relative measures of performance for np versus op specimens.201121738731
molecular basis of antigenic drift in influenza a/h3n2 strains (1968-2007) in the light of antigenantibody interactions.the emergence of new strains of influenza virus have caused several pandemics over the last hundred years with the latest being the h1n1 swine flu pandemic of 2009. the hemagglutinin (ha) protein of the influenza virus is the primary target of human immune system and is responsible for generation of protective antibodies in humans. mutations in this protein results in change in antigenic regions (antigenic drift) which consequently leads to loss of immunity in hosts even in vaccinated population ...201121738327
highly pathogenic avian influenza virus h5n1 infects alveolar macrophages without virus production or excessive tnf-alpha induction.highly pathogenic avian influenza virus (hpaiv) of the subtype h5n1 causes severe, often fatal pneumonia in humans. the pathogenesis of hpaiv h5n1 infection is not completely understood, although the alveolar macrophage (am) is thought to play an important role. hpaiv h5n1 infection of macrophages cultured from monocytes leads to high percentages of infection accompanied by virus production and an excessive pro-inflammatory immune response. however, macrophages cultured from monocytes are differ ...201121731493
compatibility of h9n2 avian influenza surface genes and 2009 pandemic h1n1 internal genes for transmission in the ferret model.in 2009, a novel h1n1 influenza (ph1n1) virus caused the first influenza pandemic in 40 y. the virus was identified as a triple reassortant between avian, swine, and human influenza viruses, highlighting the importance of reassortment in the generation of viruses with pandemic potential. previously, we showed that a reassortant virus composed of wild-type avian h9n2 surface genes in a seasonal human h3n2 backbone could gain efficient respiratory droplet transmission in the ferret model. here we ...201121730147
A novel genotyping and quantitative analysis of neuraminidase inhibitor-resistance associated mutations in influenza A viruses by single nucleotide polymorphism analysis.Neuraminidase (NA) inhibitors are among the first line of defense against influenza virus infection. With the increased worldwide use of the drugs, antiviral susceptibility surveillance is increasingly important for effective clinical management and for public health epidemiology. Effective monitoring requires effective resistance detection methods. We have developed and validated a novel genotyping method for rapid detection of established NA inhibitor resistance markers in influenza viruses by ...201121730113
influenza virus-like particle can accommodate multiple subtypes of hemagglutinin and protect from multiple influenza types and subtypes.despite existing vaccines and specific therapies, epidemics of seasonal influenza annually claim 200,000-500,000 lives worldwide. pandemic influenza represents an even greater threat, with numerous potentially pandemic viruses circulating in nature. development of multi-specific vaccines against multiple pandemic or seasonal strains is important for human health and the global economy. here we report a novel virus-like particle (vlp) platform that contains three hemagglutinin (ha) subtypes. this ...201121723354
interspecies transmission of the canine influenza h3n2 virus to domestic cats in south korea, 2010.in the last 4 years, incidences of endemic or epidemic respiratory diseases associated with canine influenza h3n2 virus in asian dogs have been reported in countries such as south korea and china. canine species were considered to be the new natural hosts for this virus. however, at the beginning of 2010, influenza-like respiratory signs, such as dyspnea, were also observed among cats as well as in dogs in an animal shelter located at seoul, south korea. the affected cats showed 100% morbidity a ...201121715595
excess mortality associated with influenza epidemics in portugal, 1980 to 2004.influenza epidemics have a substantial impact on human health, by increasing the mortality from pneumonia and influenza, respiratory and circulatory diseases, and all causes. this paper provides estimates of excess mortality rates associated with influenza virus circulation for 7 causes of death and 8 age groups in portugal during the period of 1980-2004.201121713040
overexpression of +¦-2,6 sialyltransferase stimulates propagation of human influenza viruses in vero cells.human influenza viruses are major concern as the leading cause of global pandemics. in infecting cells, they preferentially bind to sialyloligosaccharides containing terminal n-acetyl sialic acid linked to galactose by an +¦-2,6-linkage (neuac+¦2,6gal). the amount of neuac+¦2,6gal in vero cells, which are predominantly used for production of influenza vaccines over the past 30 years, may not be as high as that in epithelial cells of human respiratory tract, what leads to the suboptimal virus gro ...201121692563
a-ágel-capture assay for characterizing the sialyl-glycan selectivity of influenza viruses.sialic acids (sa) usually linked to galactose (gal) in an +¦2,6- or +¦2,3-configuration are considered the main cell receptors for influenza viruses, in particular for their hemagglutinins (ha). the typing of influenza virus ha receptor selectivity is relevant for understanding the transmissibility of avian and swine viruses to the human population. in this study we developed a simple and inexpensive gel-capture assay (gca) of the influenza virus ha receptor-binding selectivity. its principle is ...201121692561
predicting fixation tendencies of the h3n2 influenza virus by free energy calculation.influenza virus evolves to escape from immune system antibodies that bind to it. we used free energy calculations with einstein crystals as reference states to calculate the difference of antibody binding free energy (+ö+ög) induced by amino acid substitution at each position in epitope b of the h3n2 influenza hemagglutinin, the key target for antibody. a substitution with positive +ö+ög value decreases the antibody binding constant. on average an uncharged to charged amino acid substitution gen ...201121691431
neuraminidase inhibitor susceptibility of swine influenza a viruses isolated in germany between 1981 and 2008.european swine influenza a viruses donated the matrix protein 2 as well as the neuraminidase (na) gene to pandemic influenza a (h1n1) viruses that emerged in 2009. as a result, the latter became amantadine resistant and neuraminidase inhibitor (nai) susceptible. these recent developments reflecting the close connection between influenza a virus infection chains in humans and pigs urge an antiviral surveillance within swine influenza a viruses. here, nai susceptibility of 204 serologically typed ...201121688167
analysis of antigenically important residues in human influenza a virus in terms of b-cell epitopes.in this paper we undertake an analysis of the antigenicity of influenza a virus hemagglutinin. we developed a novel computational approach to the identification of antigenically active regions and showed that the amino acid substitutions between successive predominant seasonal strains form clusters that are consistent, in terms of both their location and their size, with the properties of b-cell epitopes in general and with those epitopes that have been identified experimentally in influenza a v ...201121680505
patchouli alcohol: in vitro direct anti-influenza virus sesquiterpene in pogostemon cablin benth.during the screening of anti-influenza virus substances from traditional herbal medicines, the methanol extract from the leaves of pogostemon cablin benth. showed potent in vitro antiviral activity (99.8% inhibition at a concentration of 10 μg/ml) against influenza virus a/pr/8/34 (h1n1). the anti-influenza virus principle was isolated from the hexane-soluble fraction, through solvent fractionation, repeated silica gel column chromatography, and reversed-phase hplc. the major active principle ...201121671149
estimation of type- and subtype-specific influenza vaccine effectiveness in victoria, australia using a test negative case control method, 2007-2008.antigenic variation of influenza virus necessitates annual reformulation of seasonal influenza vaccines, which contain two type a strains (h1n1 and h3n2) and one type b strain. we used a test negative case control design to estimate influenza vaccine effectiveness (ve) against influenza by type and subtype over two consecutive seasons in victoria, australia.201121669006
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