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a new class of synthetic anti-lipopolysaccharide peptides inhibits influenza a virus replication by blocking cellular attachment.influenza a viruses are a continuous threat to human health as illustrated by the 2009 h1n1 pandemic. since circulating influenza virus strains become increasingly resistant against currently available drugs, the development of novel antivirals is urgently needed. here, we have evaluated a recently described new class of broad-spectrum antiviral peptides (synthetic anti-lipopolysaccharide peptides; salps) for their potential to inhibit influenza virus replication in vitro and in vivo. we found t ...201424486207
dietary enterococcus faecium ncimb 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection.swine influenza viruses (siv) regularly cause significant disease in pigs worldwide. since there is no causative treatment of siv, we tested if probiotic enterococcus (e.) faecium ncimb 10415 or zinc (zn) oxide as feed supplements provide beneficial effects upon siv infection in piglets. seventy-two weaned piglets were fed three different diets containing either e. faecium or different levels of zn (2500 ppm, zn(high); 50 ppm, zn(low)). half of the piglets were vaccinated intramuscularly (vac) t ...201424489827
differences in antibody responses between trivalent inactivated influenza vaccine and live attenuated influenza vaccine correlate with the kinetics and magnitude of interferon signaling in children.live attenuated influenza vaccine (laiv) and trivalent inactivated influenza vaccine (tiv) are effective for prevention of influenza virus infection in children, but the mechanisms associated with protection are not well defined.201424495909
transcriptomic characterization of the novel avian-origin influenza a (h7n9) virus: specific host response and responses intermediate between avian (h5n1 and h7n7) and human (h3n2) viruses and implications for treatment options.a novel avian-origin h7n9 influenza a virus (iav) emerged in china in 2013, causing mild to lethal human respiratory infections. h7n9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. determining whether h7n9 induces a host response closer to that with human or avian iav is important in order to better characterize this emerging virus. here we compared the human lung epithelial cell response to infection with a/anhui/01/13 (h7n9) ...201424496798
integrating influenza antigenic dynamics with molecular evolution.influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (hi) assay. here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phy ...201424497547
influenza a virus infections in marine mammals and terrestrial carnivores.influenza a viruses (iav), members of the orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. the viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. the mammalian-adapted iavs originally arose by transspecies transmission from avian sources. in swine, horse and man, species-adapted iav lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly vari ...201424511825
prospective surveillance and molecular characterization of seasonal influenza in a university cohort in singapore.southeast asia is believed to be a potential locus for the emergence of novel influenza strains, and therefore accurate sentinel surveillance in the region is critical. limited information exists on sentinel surveillance of influenza-like illness (ili) in young adults in singapore in a university campus setting. the objective of the present study was to determine the proportion of ili caused by influenza a and b viruses in a university cohort in singapore.201424520371
substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza a h3n2 viruses in u.s. swine.swine influenza a virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. the hemagglutinin (ha) protein is the primary target of protective immune responses and the major component in swine influenza a vaccines. however, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in huma ...201424522915
tmprss2 is a host factor that is essential for pneumotropism and pathogenicity of h7n9 influenza a virus in mice.cleavage of the hemagglutinin (ha) by host proteases is essential for the infectivity of influenza viruses. here, we analyzed the role of the serine protease tmprss2, which activates ha in the human respiratory tract, in pathogenesis in a mouse model. replication of the human h7n9 isolate a/anhui/1/13 and of human h1n1 and h3n2 viruses was compared in tmprss2 knockout (tmprss2(-/-)) and wild-type (wt) mice. knockout of tmprss2 expression inhibited h7n9 influenza virus replication in explants of ...201424522916
phylogenetic analysis of a swine influenza a(h3n2) virus isolated in korea in 2012.influenza a virus (iav) can infect avian and mammalian species, including humans. the genome nature of iavs may contribute to viral adaptation in different animal hosts, resulting in gene reassortment and the reproduction of variants with optimal fitness. as seen again in the 2009 swine-origin influenza a h1n1 pandemic, pigs are known to be susceptible to swine, avian, and human iavs and can serve as a 'mixing vessel' for the generation of novel iav variants. to this end, the emergence of swine ...201424523938
h3n2 virus as causative agent of ards requiring extracorporeal membrane oxygenation support.pandemic influenza virus a(h1n1) 2009 was associated with a higher risk of viral pneumonia in comparison with seasonal influenza viruses. the influenza season 2011-2012 was characterized by the prevalent circulation of influenza a(h3n2) viruses. whereas most h3n2 patients experienced mild, self-limited influenza-like illness, some patients were at increased risk for influenza complications because of age or underlying medical conditions. cases presented were patients admitted to the intensive ca ...201424527039
live attenuated influenza vaccine enhances colonization of streptococcus pneumoniae and staphylococcus aureus in mice.community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. what has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (laivs). using a mouse-adapted laiv against influenza a (h3n2) virus carrying the same mutations as the human flumist vaccine, we find that laiv vacc ...201424549845
in vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against influenza virus isolates in the 2011-2012 season in japan.the neuraminidase inhibitors oseltamivir phosphate (tamiflu®), zanamivir (relenza®), laninamivir octanoate (inavir®), and peramivir (rapiacta®) have been available for the treatment of influenza in japan since 2010. to assess the extent of viral resistance, we measured the 50% inhibitory concentration (ic₅₀) of each drug for influenza virus isolates from the 2011-2012 influenza season. specimens were obtained from patients prior to treatment. viral isolation was done using madine-darby canine ki ...201424560563
intranasal vaccination with a replication-deficient influenza virus induces heterosubtypic neutralising mucosal iga antibodies in humans.we investigated the cross-neutralising potential of serum and nasal wash samples from volunteers who were intranasally immunised once with a monovalent replication-deficient delns1-h1n1 influenza virus vaccine (7.7log10tcid50/volunteer). eight out of twelve (8/12) vaccinees responded to vaccination with a significant increase of antibody levels in serum igg elisa, mucosal iga elisa, mna or hai. four responders showed delns1-specific elisa iga increases and revealed excellent homosubtypic neutral ...201424560674
viral aetiology influenza like illnesses in santa cruz, bolivia (2010-2012).acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of influenza like illnesses (ilis) remain largely unknown in developing countries. this study represents the first attempt to characterise viral aetiologies of ilis in bolivia.201424564892
evaluation of screening assays for the detection of influenza a virus serum antibodies in swine.increased surveillance of influenza a virus (iav) infections in human and swine populations is mandated by public health and animal health concerns. antibody assays have proven useful in previous surveillance programmes because antibodies provide a record of prior exposure and the technology is inexpensive. the objective of this research was to compare the performance of influenza serum antibody assays using samples collected from pigs (vaccinated or unvaccinated) inoculated with either a/swine/ ...201624571447
a predictive fitness model for influenza.the seasonal human influenza a/h3n2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. two factors are shown to determ ...201424572367
synthesis and anti-influenza activities of novel baicalein analogs.a series of novel flavones derivatives were synthesized based on modification of the active ingredients of a traditional chinese medicine scutellaria baicalensis georgi and screened for anti-influenza activity. the synthetic baicalein (flavone) analogs, especially with the b-rings substituted with bromine atoms, were much more potent than oseltamivir or ribavirin against h1n1 tamiflu-resistant (h1n1 tr) virus and usually with more favorable selectivity. the most promising were 5b, 5c, 6b and 6c, ...201424572377
(19)f nmr reveals multiple conformations at the dimer interface of the nonstructural protein 1 effector domain from influenza a virus.nonstructural protein 1 of influenza a virus (ns1a) is a conserved virulence factor comprised of an n-terminal double-stranded rna (dsrna)-binding domain and a multifunctional c-terminal effector domain (ed), each of which can independently form symmetric homodimers. here we apply (19)f nmr to ns1a from influenza a/udorn/307/1972 virus (h3n2) labeled with 5-fluorotryptophan, and we demonstrate that the (19)f signal of trp187 is a sensitive, direct monitor of the ed helix:helix dimer interface. ( ...201424582435
oseltamivir-zanamivir combination therapy is not superior to zanamivir monotherapy in mice infected with influenza a(h3n2) and a(h1n1)pdm09 viruses.the efficacy of oseltamivir-zanamivir combination therapy compared to that of monotherapy was evaluated in mice infected with influenza a(h3n2) or a(h1n1)pdm09 viruses. for a(h3n2) virus, zanamivir monotherapy and oseltamivir-zanamivir combination showed significant reduction of mean weight loss compared to oseltamivir. zanamivir monotherapy also conferred decreased mortality, weight loss and lung viral titers (lvt) compared to oseltamivir for a(h1n1)pdm09 wild-type virus. intermediate benefits ...201424583158
1,2,3-triazole-containing derivatives of rupestonic acid: click-chemical synthesis and antiviral activities against influenza viruses.two series of rupestonic acid derivatives, (1-substituted-1h-1,2,3-triazol-4-yl)methyl 2-((5r,8s,8as)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylate and n-(1-substituted-1h-1,2,3-triazol-4-yl)methyl 2-((5r,8s,8as)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylamide were easily and efficiently synthesized via click chemistry. these compounds were tested for their in vitro activities against various strains of influenza a virus (h1n1, oseltamivir resistant h1n1, ...201424583605
supplementation of influenza split vaccines with conserved m2 ectodomains overcomes strain specificity and provides long-term cross protection.current influenza vaccines do not provide good protection against antigenically different influenza a viruses. as an approach to overcome strain specificity of protection, this study demonstrates significantly improved long-term cross protection by supplementing split vaccines with a conserved molecular target, a repeat of the influenza m2 ectodomain (m2e) expressed on virus-like particles (m2e5x vlps) in a membrane-anchored form. intramuscular immunization with h1n1 split vaccine (a/california/ ...201424590045
a phospha-oseltamivir-biotin conjugate as a strong and selective adhesive for the influenza virus.we present the synthesis and application of a molecule containing both the powerful influenza neuraminidase (na) inhibitor phospha-oseltamivir and d-biotin, connected via an undecaethylene glycol spacer. it inhibits influenza virus neuraminidase (from the h3n2 x31 virus) in the same range as oseltamivir, with a slow off-rate, and produces a stable na-coated surface when loaded onto streptavidin-coated biosensors. purified x31 virus binds to these loaded biosensors with an apparent dissociation c ...201424594352
emergence of g186d mutation in the presence of r292k mutation in an immunocompromised child infected with influenza a/h3n2 virus, treated with oseltamivir.an immunocompromised child with influenza a/h3n2 virus infection, treated with oseltamivir from day 1, had nasal swabs taken on days 1, 4, 7, and 10 of the illness. pyrosequencing showed increasing proportions of viruses with r292k (neuraminidase gene) and g186d (hemagglutinin gene) mutations, resulting in a viral load rebound by day 10.201424599981
the host protease tmprss2 plays a major role in in vivo replication of emerging h7n9 and seasonal influenza viruses.proteolytic cleavage of the hemagglutinin (ha) protein is essential for influenza a virus (iav) to acquire infectivity. this process is mediated by a host cell protease(s) in vivo. the type ii transmembrane serine protease tmprss2 is expressed in the respiratory tract and is capable of activating a variety of respiratory viruses, including low-pathogenic (lp) iavs possessing a single arginine residue at the cleavage site. here we show that tmprss2 plays an essential role in the proteolytic activ ...201424600012
impact of 2009 pandemic influenza among vietnamese children based on a population-based prospective surveillance from 2007 to 2011.influenza virus is one of the major viral pathogens causing pediatric acute respiratory infection (ari). the spread of pandemic influenza a (a(h1n1)pdm09) in 2009 around the globe had a huge impact on global health.201424602158
metal enhanced fluorescence on nanoporous gold leaf-based assay platform for virus detection.in the present study, a rapid, sensitive and quantitative detection of influenza a virus targeting hemagglutinin (ha) was developed using hybrid structure of quantum dots (qds) and nanoporous gold leaf (npgl). npgl film was prepared by dealloying bimetallic film where its surface morphology and roughness were fairly controlled. anti-influenza a virus ha antibody (ab66189) was bound with npgl and amine (-nh2) terminated qds. these biofunctionalized npgl and qds formed a complex with the influenza ...201424607620
preexisting cd4+ t-cell immunity in human population to avian influenza h7n9 virus: whole proteome-wide immunoinformatics analyses.in 2013, a novel avian influenza h7n9 virus was identified in human in china. the antigenically distinct h7n9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. epitope-specific preexisting t-cell immunity was one of the protective mechanisms in pandemic 2009 h1n1 even in the absence of cross-protective antibodies. hence, the assessment of preexisting cd4+ t-cell immunity to conserved epitopes shared between h7n9 and human influenza a viruses (iav) is c ...201424609014
stability of neuraminidase in inactivated influenza vaccines.influenza vaccines are effective in protecting against illness and death caused by this seasonal pathogen. antibodies that block the function of either hemagglutinin (ha) or neuraminidase (na) contribute to vaccine efficacy, however vaccine potency is based only on ha content. na protein content in vaccines varies from season to season due to differences in the relative amounts of ha and na in influenza a, h1n1 and h3n2, and influenza b viruses that are selected for each manufacturing campaign. ...201424613525
detection of nonhemagglutinating influenza a(h3) viruses by enzyme-linked immunosorbent assay in quantitative influenza virus culture.to assess the efficacy of novel antiviral drugs against influenza virus in clinical trials, it is necessary to quantify infectious virus titers in respiratory tract samples from patients. typically, this is achieved by inoculating virus-susceptible cells with serial dilutions of clinical specimens and detecting the production of progeny virus by hemagglutination, since influenza viruses generally have the capacity to bind and agglutinate erythrocytes of various species through their hemagglutini ...201424622097
mucosal immunization with a candidate universal influenza vaccine reduces virus transmission in a mouse model.pandemic influenza is a major public health concern, but conventional strain-matched vaccines are unavailable early in a pandemic. candidate "universal" vaccines targeting the viral antigens nucleoprotein (np) and matrix 2 (m2), which are conserved among all influenza a virus strains and subtypes, could be manufactured in advance for use at the onset of a pandemic. these vaccines do not prevent infection but can reduce disease severity, deaths, and virus titers in the respiratory tract. we hypot ...201424623430
influenza vaccine effectiveness in spain 2013/14: subtype-specific early estimates using the cyceva study.adjusted early estimates of the 2013/14 influenza vaccine effectiveness (ve) in spain for all age groups was 35% (95% ci: -9 to 62), 33% (95% ci: -33 to 67) and 28% (95% ci: -33 to 61) against any influenza virus type, a(h1n1)pdm09 and a(h3n2) viruses, respectively. for the population targeted for vaccination, the adjusted ve was 44% (95% ci: -11 to 72), 36% (95% ci: -64 to 75) and 42% (95% ci: -29 to 74), respectively. these preliminary results in spain suggest a suboptimal protective effect of ...201424626206
purification of vero cell derived live replication deficient influenza a and b virus by ion exchange monolith chromatography.we explored the possibilities for purification of various δns1 live, replication deficient influenza viruses on ion exchange methacrylate monoliths. influenza a δns1-h1n1, δns1-h3n2, δns1-h5n1 and δns1-influenza b viruses were propagated in vero cells and concentrated by tangential flow filtration. all four virus strains adsorbed well to cim qa and cim deae anion exchangers, with cim qa producing higher recoveries than cim deae. δns1-influenza a viruses adsorbed well also to cim so3 cation excha ...201424631091
[development and validation of the real-time pcr assay for the identification of viral agents causing acute respiratory infections in humans].the real time pcr assay targeting influenza a and b virus, 5 subtypes of influenza a virus (seasonal h1n1, pandemic h1n1 (2009), seasonal h3n2, pathogenic for human subtypes of avian influenza h5 and h7), respiratory syncytial virus, and adenovirus was developed. the analytical sensitivity of the developed assay was 1 x 10(3) genome equivalents per ml. the diagnostic sensitivity of the method was 1 x l0(3)-10(4) viral particles per ml. experiments with human dna/cdna and viral cdna showed a mark ...201324645276
development of rapid immunochromatographic test for hemagglutinin antigen of h7 subtype in patients infected with novel avian influenza a (h7n9) virus.since human infection with the novel h7n9 avian influenza virus was identified in china in march 2013, the relatively high mortality rate and possibility of human-to-human transmission have highlighted the urgent need for sensitive and specific assays for diagnosis of h7n9 infection.201424647358
rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.live attenuated influenza vaccine viruses (laivs) can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated master donor virus (mdv) and a seasonal wild-type (wt) virus. the vaccine candidates contain hemagglutinin (ha) and neuraminidase (na) genes derived from the circulating wt viruses and the remaining six genes derived from the mdv strains. rapid, efficient selection of the viruses with 6∶2 genome compositions from the large numb ...201424647786
cluster of influenza a cases in vaccinated population of adults in virology laboratory in glasgow in december 2012.the majority of influenza infections during the 2012/2013 influenza season in scotland have been due to influenza a h3n2. we report an outbreak of influenza a h3n2 in a vaccinated population of adults in the regional virology laboratory in glasgow. this investigation was carried out to confirm the epidemiological link between cases.201424659378
in vitro antiviral activity of a series of wild berry fruit extracts against representatives of picorna-, orthomyxo- and paramyxoviridae.wild berry species are known to exhibit a wide range of pharmacological activities. they have long been traditionally applied for their antiseptic, antimicrobial, cardioprotective and antioxidant properties. the aim of the present study is to reveal the potential for selective antiviral activity of total methanol extracts, as well as that of the anthocyanins and the non-anthocyanins from the following wild berries picked in bulgaria: strawberry (fragaria vesca l.) and raspberry (rubus idaeus l.) ...201424660461
reserve autophagic capacity in alveolar epithelia provides a replicative niche for influenza a virus.autophagy contributes to cellular homeostasis through metabolite recycling and degradation of cytotoxic protein aggregates and damaged organelles. although recent studies have established that the requirement for basal autophagy is largely tissue specific, the importance of autophagy for alveolar epithelial cell homeostasis remains an important knowledge gap. in the present study we generated two mouse models, with > 90% or > 50% recombination at the atg5 locus in the distal respiratory epitheli ...201424661119
one-health simulation modelling: a case study of influenza spread between human and swine populations using naadsm.the circulation of zoonotic influenza a viruses including ph1n1 2009 and h5n1 continue to present a constant threat to animal and human populations. recently, an h3n2 variant spread from pigs to humans and between humans in limited numbers. accordingly, this research investigated a range of scenarios of the transmission dynamics of ph1n1 2009 virus at the swine-human interface while accounting for different percentages of swine workers initially immune. furthermore, the feasibility of using naad ...201624661802
retrospective serology study of respiratory virus infections in captive great apes.great apes are extremely sensitive to infections with human respiratory viruses. in this study, we retrospectively analyzed sera from captive chimpanzees, gorillas and orang-utans. more than 1000 sera (403 chimpanzee, 77 gorilla, and 535 orang-utan sera) were analyzed for antibodies to the human respiratory viruses rsv (respiratory syncytial virus, hmpv (human metapneumovirus), h1n1 and h3n2 influenza a viruses, and influenza b virus. in all ape species high seroprevalences were found for rsv, h ...201424662675
influenza virus h1n1 activates platelets through fcγriia signaling and thrombin generation.platelets play crucial functions in hemostasis and the prevention of bleeding. during h1n1 influenza a virus infection, platelets display activation markers. the platelet activation triggers during h1n1 infection remain elusive. we observed that h1n1 induces surface receptor activation, lipid mediator synthesis, and release of microparticles from platelets. these activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). considering that immune ...201424665136
low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted h3n2 vaccine strain not antigenic drift in circulating viruses.influenza vaccine effectiveness (ve) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. during the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low ve was instead related to mutations in the egg-adapted h3n2 vaccine strain rather than antigenic drift in circulating viruses.201424667168
protective efficacy of a high-growth reassortant swine h3n2 inactivated vaccine constructed by reverse genetic manipulation.novel reassortant h3n2 swine influenza viruses (swiv) with the matrix gene from the 2009 h1n1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the united states, indicating that h3n2 swiv might be a potential threat to public health. since southern china is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring h3n2 subtype swiv infections, and thus limit the possibility of swiv infection at ...201424675833
full-genome sequences of influenza h3n2 virus strains isolated from finnish patients during the 2012-2013 epidemic season.here, we sequenced 10 influenza a(h3n2) virus genomes isolated from finnish patients diagnosed with flu-like illness during the 2012-2013 influenza season. the alignment showed a high number of amino acid substitutions (238 in total) in only 10 samples, proving that a high mutation rate exists in seasonal influenza a viruses.201424675845
association between antibody titers and protection against influenza virus infection within households.previous studies have established that antibody titer measured by the hemagglutination-inhibiting (hai) assay is correlated with protection against influenza virus infection, with an hai titer of 1:40 generally associated with 50% protection.201424676208
protective effect of fluvastatin on influenza virus infection.statins are 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors and have pleiotropic effects. it has been suggested that statins may be a potential treatment during the next influenza pandemic. in a previous study we found that a statin/caffeine combination protects balb/c mice against influenza a, subtypes haemagglutinin type 5 and neuraminidase type 1 (h5n1), h3n2 and h1n1 infection. the effect of statins alone on influenza virus infection, however, is not known. in this study, it was i ...201424676773
phylogeny of spanish swine influenza viruses isolated from respiratory disease outbreaks and evolution of swine influenza virus within an endemically infected farm.in the present study, outbreaks of respiratory disease were investigated for the presence of swine influenza virus (siv). in 14 cases the circulating siv strains were isolated, fully sequenced and compared with other known sivs. the viruses causing the outbreaks belonged to the h1n1 (including human pandemic h1n1), h3n2 and h1n2 subtypes. in 11/14 cases the phylogenetic analyses indicated the occurrence of probable reassortment events. in the second part of the study, the genetic evolution of h1 ...201424685238
pestalols a-e, new alkenyl phenol and benzaldehyde derivatives from endophytic fungus pestalotiopsis sp. acbc2 isolated from the chinese mangrove plant aegiceras corniculatum.five alkenyl phenol and benzaldehyde derivatives, pestalols a-e (1-5), as well as seven known compounds (6-12), were isolated from endophytic fungus pestalotiopsis sp. acbc2 derived from the chinese mangrove plant aegiceras corniculatum. their structures were determined by spectroscopic analyses. compounds 2 and 3 showed cytotoxicity against a panel of 10 tumor cell lines. compounds 1-5, 8, 9, 11, and 12 showed inhibitory activities against influenza a virus subtype (h3n2) and swine flu (h1n1) v ...201424690916
a broadly neutralizing human monoclonal antibody directed against a novel conserved epitope on the influenza virus h3 hemagglutinin globular head.most neutralizing antibodies elicited during influenza virus infection or vaccination target immunodominant, variable epitopes on the globular head region of hemagglutinin (ha), which leads to narrow strain protection. in this report, we describe the properties of a unique anti-ha monoclonal antibody (mab), d1-8, that was derived from human b cells and exhibits potent, broad neutralizing activity across antigenically diverse influenza h3 subtype viruses. based on selection of escape variants, we ...201424696468
development of high-throughput liquid chips for respiratory virus detection.diagnosis of viral respiratory tract infections clinically is often nonspecific, and a rapid, high-throughput laboratory technique which can detect major respiratory viruses is desirable.201424697109
influenza a h1n1 pandemic strain evolution--divergence and the potential for antigenic drift variants.the emergence of a novel a(h1n1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. we examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (ha), neuraminidase (na), and nucleoprotein (np) segments of the a(h1n1)pdm09 strain using publicly available data. we calculated the nucleotide and amino acid hamming distance f ...201424699432
a humoral immunity survey following the 2012 influenza season after the ph1n1 pandemic in guangzhou, china.according to pathogenic surveillance data during the first half of 2012, the h3n2 influenza virus was prevalent in guangdong, china, but no pandemic h1n1 (ph1n1) virus was detected. this study aimed to measure the seroprevalence of ph1n1 and h3n2 infection following the influenza epidemic in 2012. we collected serum samples by stratified random sampling in a cross-sectional survey from august, 2012 to october, 2012. antibody titers against h3n2, ph1n1, and influenza b antigens were measured by t ...201424702517
mutations flanking the carbohydrate binding site of surfactant protein d confer antiviral activity for pandemic influenza a viruses.we recently reported that a trimeric neck and carbohydrate recognition domain (ncrd) fragment of human surfactant protein d (sp-d), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (d325a+r343v) exhibits markedly increased antiviral activity for seasonal strains of influenza a virus (iav). the ncrd binds to glycan-rich viral envelope proteins including hemagglutinin (ha). we now show that replacement of d325 with serine to create d325s+r343v provided equal or ...201424705721
il-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires cd4+ t cells for heterosubtypic protection.current influenza vaccines are ineffective against novel viruses and the source or the strain of the next outbreak of influenza is unpredictable; therefore, establishing universal immunity by vaccination to limit the impact of influenza remains a high priority. to meet this challenge, a novel vaccine has been developed using the immunogenic live vaccinia virus as a vaccine vector, expressing multiple h5n1 viral proteins (ha, na, m1, m2, and np) together with il-15 as a molecular adjuvant. previo ...201424706798
prevalence and correlates of influenza-a in piggery workers and pigs in two communities in lagos, nigeria.worldwide, three influenza-a virus subtypes (h1n1, h1n2 and h3n2) in swine are major public health issues. in nigeria, the existence of these subtypes in pigs has not been well studied. this study aimed at determining the prevalence and correlates of influenza-a viruses circulating in piggery workers and pigs in oke-aro and goshen communities in lagos, nigeria.201324711881
innate immune response to a h3n2 subtype swine influenza virus in newborn porcine trachea cells, alveolar macrophages, and precision-cut lung slices.viral respiratory diseases remain of major importance in swine breeding units. swine influenza virus (siv) is one of the main known contributors to infectious respiratory diseases. the innate immune response to swine influenza viruses has been assessed in many previous studies. however most of these studies were carried out in a single-cell population or directly in the live animal, in all its complexity. in the current study we report the use of a trachea epithelial cell line (newborn pig trach ...201424712747
epidemiological aspects of influenza a related to climatic conditions during and after a pandemic period in the city of salvador, northeastern brazil.during the influenza pandemic of 2009, the a(h1n1)pdm09, a/h3n2 seasonal and influenza b viruses were observed to be co-circulating with other respiratory viruses. to observe the epidemiological pattern of the influenza virus between may 2009-august 2011, 467 nasopharyngeal aspirates were collected from children less than five years of age in the city of salvador. in addition, data on weather conditions were obtained. indirect immunofluorescence, real-time transcription reverse polymerase chain ...201424714967
receptor mimicry by antibody f045-092 facilitates universal binding to the h3 subtype of influenza virus.influenza viruses present a significant health challenge each year, as in the h3n2 epidemic of 2012-2013. here we describe an antibody, f045-092, that possesses broadly neutralizing activity against the entire h3 subtype and accommodates the natural variation and additional glycosylation in all strains tested from 1963 to 2011. crystal structures of f045-092 in complex with has from 1975 and 2011 h3n2 viruses reveal the structural basis for its neutralization breadth through insertion of its 23- ...201424717798
conserved neutralizing epitope at globular head of hemagglutinin in h3n2 influenza viruses.neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-ph-induced conformational change in hemagglutinin required for membrane fusion. in general, the former type of antibody binds to the globular head formed by ha1 and has narrow strain specificity, while the latter type binds to the stem mainly formed by ha2 and has broad strain specificity. in the present study, we analyzed the epitope and funct ...201424719430
assessment of seasonality of influenza in swine using field submissions to a diagnostic laboratory in ontario between 2007 and 2012.seasonality of any infectious disease is important for its control and monitoring. while influenza seasonality in people has been evaluated extensively, this question has not been studied well in swine populations.201424725968
duration of the protective immune response after prime and booster vaccination of yearlings with a live modified cold-adapted viral vaccine against equine influenza.we previously created a live vaccine against equine influenza based the new reassortant cold-adapted (ca) strain a/hk/otar/6:2/2010. the live vaccine contains surface proteins (ha, na) from the wild-type virus a/equine/otar/764/2007 (н3n8; american lineage florida clade 2), and internal proteins (pb2, pb1, pa, np, m, ns) from the attenuated ca donor virus a/hong kong/1/68/162/35ca (h3n2). to determine the safety and duration of the protective immune responses, 90 yearlings were intranasally vacc ...201424726250
influenza h1n1pdm-specific maternal antibodies offer limited protection against wild-type virus replication and influence influenza vaccination in ferrets.the objective was to study passively acquired influenza h1n1 pandemic (h1n1pdm) maternal antibody kinetics and its impact on subsequent influenza infection and vaccination in ferrets during an outbreak of the h1n1pdm.201424734293
analysis of the acute-phase protein response in pigs to clinical and subclinical infection with h3n2 swine influenza virus.swine influenza (si) is a contagious, important respiratory disease. diagnosis of si is based on the clinical signs, confirmed by the detection of viral rna or specific antibodies. however, the infection is much more frequent than the disease.201424734294
safety and immunogenicity of a vero cell culture-derived whole-virus h5n1 influenza vaccine in chronically ill and immunocompromised patients.the development of vaccines against h5n1 influenza a viruses is a cornerstone of pandemic preparedness. clinical trials of h5n1 vaccines have been undertaken in healthy subjects, but studies in risk groups have been lacking. in this study, the immunogenicity and safety of a nonadjuvanted cell culture-derived whole-virus h5n1 vaccine were assessed in chronically ill and immunocompromised adults. subjects received two priming immunizations with a clade 1 a/vietnam h5n1 influenza vaccine, and a sub ...201424739978
intrahost dynamics of influenza virus reassortment.the segmented nature of the influenza virus genome allows reassortment between coinfecting 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 coinfected guinea pigs over time a ...201424741099
substantial morbidity and mortality associated with pandemic a/h1n1 influenza in mexico, winter 2013-2014: gradual age shift and severity.a recrudescent wave of pandemic influenza a/h1n1 is underway in mexico in winter 2013-14, following a mild 2012-13 a/h3n2 influenza season. mexico previously experienced several waves of pandemic a/h1n1 activity in spring, summer and fall 2009 and winter 2011-2012, with a gradual shift of influenza-related hospitalizations and deaths towards older ages. here we describe changes in the epidemiology of the 2013-14 a/h1n1 influenza outbreak, relative to previous seasons dominated by the a/h1n1 pand ...201424744975
development of a reverse transcription loop-mediated isothermal amplification assay for the rapid diagnosis of avian influenza a (h7n9) virus infection.a genetic diagnosis system for detecting avian influenza a (h7n9) virus infection using reverse transcription-loop-mediated isothermal amplification (rt-lamp) technology was developed. the rt-lamp assay showed no cross-reactivity with seasonal influenza a (h3n2 and h1n1pdm09) or influenza b viruses circulating in humans or with avian influenza a (h5n1) viruses. the sensitivity of the rt-lamp assay was 42.47 copies/reaction. considering the high specificity and sensitivity of the assay for detect ...201424747008
molecular characterization and phylogenetic analysis of h3 subtype avian influenza viruses isolated from domestic ducks in zhejiang province in china.in 2013, 15 avian influenza viruses (aivs), h3n2 (n = 7), h3n3 (n = 3), h3n6 (n = 3), and h3n8 (n = 2), were isolated from domestic ducks in zhejiang province in china. these strains were characterized by whole genome sequencing with subsequent phylogenetic analysis and genetic comparison. phylogenetic analysis of all eight viral genes showed that these strains clustered in the aiv eurasian lineage. analysis of the neuraminidase (na) gene indicates that a re-assortment event between h3 and h9n2 ...201424748106
reassortant swine influenza viruses isolated in japan contain genes from pandemic a(h1n1) 2009.in 2013, three reassortant swine influenza viruses (sivs)-two h1n2 and one h3n2-were isolated from symptomatic pigs in japan; each contained genes from the pandemic a(h1n1) 2009 virus and endemic sivs. phylogenetic analysis revealed that the two h1n2 viruses, a/swine/gunma/1/2013 and a/swine/ibaraki/1/2013, were reassortants that contain genes from the following three distinct lineages: (i) h1 and nucleoprotein (np) genes derived from a classical swine h1 ha lineage uniquely circulating among ja ...201424750464
influenza a subtype h3 viruses in feral swine, united states, 2011-2012.to determine whether, and to what extent, influenza a subtype h3 viruses were present in feral swine in the united states, we conducted serologic and virologic surveillance during october 2011-september 2012. these animals were periodically exposed to and infected with a(h3n2) viruses, suggesting they may threaten human and animal health.201424751326
akt inhibitor mk2206 prevents influenza ph1n1 virus infection in vitro.the influenza ph1n1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. here we show that the akt inhibitor mk2206 blocks influenza ph1n1 virus infection in vitro. in particular, at noncytotoxic concentrations, mk2206 alters akt signaling and inhibits endocytic uptake of the virus. interestingly, mk2206 is unable to inhibit h3n2, ...201424752266
managing seasonal influenza: oseltamivir treatment policy in indonesia?to manage cases of avian influenza a/h5n1 virus infection and in anticipation of a pandemic triggered by this virus, indonesia purchased and distributed oseltamivir to the government health facilities. oseltamivir is an antiviral drug that was developed for the treatment of influenza infections. disease surveillance and research suggests that seasonal influenza (a/h1n1, a/h3n2 or b) results in considerable morbidity and mortality in indonesia, where over 15% of influenza-like illness and severe ...201424760811
emergence of truncated pb1-f2 protein of h3n2 influenza virus during its epidemic period in jiangsu province, china.pb1-f2 protein has been proven to increase the pathogenicity of influenza a virus (iav) strains in primary infection and in secondary bacterial infection. it can also regulate the activity of viral polymerase. however, it was shown in another retrospective study that a portion of iavs do not express full-length pb1-f2 protein during virus development; different kinds of stop codons cause exits in the open reading frames and form pb1-f2 gene products with the corresponding genotypes. truncated pb ...201424762594
[evolution of influenza a(h3n2) virus from 2007 to 2012].the results of the genetic studies of influenza viruses make it possible to understand their evolution and recommendations for vaccine strains content. in this work, the data of complete sequence of the ha, na, and m2-protein for 34 strains of influenza a(h3n2) virus circulating in russia during 2007-2012 are presented. the influenza strains were isolated in ivanovsky institute of virology, moscow, and some collaborating russian centers. the results of the phylogenetic analysis showed the differ ...201624772643
[immunization with live attenuated a/h5n1 vaccine protects guinea pigs from reinfection].cold-adapted influenza virus a/hk/1/68/162/35(h3n2) was developed as unified donor of attenuation and high reproductive capacity forvaccine strains. the reassortant of this donor with surface antigens of highly pathogenic strain alchicken/astana/6/05 (h5n1) was tested in guinea pigs as a live or inactivated preparation. immunization with both formulations induced equal levels of serum virus specific antibodies, while the level of mucosal antibodies was significantly higher in animals immunized w ...201624772645
performance of ehealth data sources in local influenza surveillance: a 5-year open cohort study.there is abundant global interest in using syndromic data from population-wide health information systems--referred to as ehealth resources--to improve infectious disease surveillance. recently, the necessity for these systems to achieve two potentially conflicting requirements has been emphasized. first, they must be evidence-based; second, they must be adjusted for the diversity of populations, lifestyles, and environments.201424776527
molecular characterization of circulating pandemic strains of influenza a virus during 2012 to 2013 in lucknow (india).the pandemic h1n1 strain of influenza a virus [a(h1n1)pdm09] is now well adapted in human populations. however, it is still causing sporadic outbreaks worldwide with different severity. the present study was planned to understand the genetic diversity (based on the ha1 gene) of influenza a(h1n1)pdm09 strains circulating during the post pandemic period. the ha1 gene was selected because the ha1 protein is immunogenic, functions as a receptor binding site and indirectly affects transmission and pa ...201424777528
a zanamivir dimer with prophylactic and enhanced therapeutic activity against influenza viruses.emerging drug resistance to antiviral therapies is an increasing challenge for the treatment of influenza virus infections. one new antiviral compound, bta938, a dimeric derivative of the viral neuraminidase inhibitor zanamivir, contains a 14-carbon linker bridging two zanamivir moieties. in these studies, we evaluated antiviral efficacy in cell cultures infected with influenza virus and in mouse models of lethal influenza using h1n1pdm09, h3n2 and oseltamivir-resistant (h275y) viruses.201424777908
genesis and pathogenesis of the 1918 pandemic h1n1 influenza a virus.the source, timing, and geographical origin of the 1918-1920 pandemic influenza a virus have remained tenaciously obscure for nearly a century, as have the reasons for its unusual severity among young adults. here, we reconstruct the origins of the pandemic virus and the classic swine influenza and (postpandemic) seasonal h1n1 lineages using a host-specific molecular clock approach that is demonstrably more accurate than previous methods. our results suggest that the 1918 pandemic virus originat ...201424778238
the rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model.dendritic cells (dcs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. the aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (lalns) in the model of a non-human primate (nhp) infected by influenza a virus (iav). cynomolgus macaques were infected with influenza a virus (h3n2) via bronchosco ...201624780366
population-based hospitalization burden of influenza a virus subtypes and antigenic drift variants in children in hong kong (2004-2011).we aim to document and analyze influenza hospitalization burden in light of antigenic changes in circulating influenza viruses in hong kong.201424786780
aminoadamantanes with persistent in vitro efficacy against h1n1 (2009) influenza a.a series of 2-adamantanamines with alkyl adducts of various lengths were examined for efficacy against strains of influenza a including those having an s31n mutation in m2 proton channel that confer resistance to amantadine and rimantadine. the addition of as little as one ch2 group to the methyl adduct of the amantadine/rimantadine analogue, 2-methyl-2-aminoadamantane, led to activity in vitro against two m2 s31n viruses a/calif/07/2009 (h1n1) and a/pr/8/34 (h1n1) but not to a third a/ws/33 (h1 ...201424793875
synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1h)-ones.a target-free approach was applied to discover anti-influenza viral compounds, where influenza infected madin-darby canine kidney cells were treated 7500 different small organic chemicals individually and reduction of virus-induced cytopathic effect was measured. one of the hit compounds was (z)-1-((5-fluoro-1h-indol-3-yl)methylene)-6-methyl-4-thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1h)-one (15a) with half-maximal effective concentrations of 17.4-21.1μm against influenza a/h1n1, a/h3n2 and b viru ...201424794525
serological and virological surveillance of avian influenza a virus h9n2 subtype in humans and poultry in shanghai, china, between 2008 and 2010.we report the serological evidence of low-pathogenic avian influenza (lpai) h9n2 infection in an occupational poultry-exposed population and a general population. a serological survey of an occupational poultry-exposed population and a general population was conducted using a haemagglutinin-inhibiting (hi) assay in shanghai, china, from january 2008 to december 2010. evidence of higher anti-h9 antibodies was found in serum samples collected from poultry workers. during this period, 239 h9n2 avia ...201524803167
novel avian influenza a (h7n9) virus induces impaired interferon responses in human dendritic cells.in march 2013 a new avian influenza a(h7n9) virus emerged in china and infected humans with a case fatality rate of over 30%. like the highly pathogenic h5n1 virus, h7n9 virus is causing severe respiratory distress syndrome in most patients. based on genetic analysis this avian influenza a virus shows to some extent adaptation to mammalian host. in the present study, we analyzed the activation of innate immune responses by this novel h7n9 influenza a virus and compared these responses to those i ...201424804732
suppressor of cytokine signaling 4 (socs4) protects against severe cytokine storm and enhances viral clearance during influenza infection.suppressor of cytokine signaling (socs) proteins are key regulators of innate and adaptive immunity. there is no described biological role for socs4, despite broad expression in the hematopoietic system. we demonstrate that mice lacking functional socs4 protein rapidly succumb to infection with a pathogenic h1n1 influenza virus (pr8) and are hypersusceptible to infection with the less virulent h3n2 (x31) strain. in socs4-deficient animals, this led to substantially greater weight loss, dysregula ...201424809749
identification of four genotypes of h3n2 swine influenza virus in pigs from southern china.in 2011, four h3n2 swine influenza viruses (sivs) were isolated from nasal swabs of four pigs (800 nasal swabs were collected from pigs showing influenza-like symptoms) in guangdong province, china. four different genotypes of h3n2 appeared among pigs in southern china, including wholly human-like h3n2 viruses, intermediate (1975) double-reassortant human h3n2 viruses (resulting from reassortment between an early human lineage and a recent human lineage), recent double-reassortant human h3n2 vir ...201424810098
comparison of the characteristics of elderly influenza patients in two consecutive seasons.the seasonality of influenza infections can be affected by virus subtypes, climate, and social networking in populations. while these factors are well known, their relative influences in specific age groups have not been fully investigated. during 2010-2011, patients aged 65 years and above with influenza virus infections were recruited from a regional hospital in hong kong. they were either residents of homes for the elderly (n=60) or living with their family (n=75). two seasons were distinguis ...201424815741
[determination of the frequency of human bocavirus and other respiratory viruses among 0-2 years age group children diagnosed as acute bronchiolitis].acute bronchiolitis, mostly seen in infants and younger children, is a lower respiratory tract infection frequently caused by viral agents. we aimed to determine the frequency of a broad panel of respiratory viruses including human bocavirus (hbov) and to assess the clinical characteristics of acute bronchiolitis in a group of children under 24 months of age. a total of 62 children (45 male, 17 female; age range: 0-2 years) with the initial diagnosis of acute bronchiolitis and 33 healthy childre ...201424819262
influenza virus genotypes circulating in and around lucknow, uttar pradesh, india, during post pandemic period, august 2010--september 2012.during the post influenza pandemic period, continuous surveillance of influenza virus and its subtypes is mandatory to help the policy makers to take effective and appropriate decisions. therefore, this study was planned to determine the pattern of influenza virus activity in context to various meteorological and clinical parameters in and around lucknow, uttar pradesh, india, during post pandemic period august 2010 - september 2012.201424820836
incidence of influenza virus infections in children in hong kong in a 3-year randomized placebo-controlled vaccine study, 2009-2012.school-aged children suffer high rates of influenza virus infections and associated illnesses each year, and are a major source of transmission in the community. however, information on the cumulative incidence of infection in specific epidemics is scarce, and there are limited studies with sufficient follow-up to identify the strength and duration of protection against reinfection.201424825868
effectiveness of seasonal influenza vaccinations against laboratory-confirmed influenza-associated infections among singapore military personnel in 2010-2013.limited information is available about seasonal influenza vaccine effectiveness (ve) in tropical communities.201424828687
n-glycolylneuraminic acid on human epithelial cells prevents entry of influenza a viruses that possess n-glycolylneuraminic acid binding ability.some animal influenza a viruses (iavs) bind not only to n-acetylneuraminic acid (neu5ac) but also to n-glycolylneuraminic acid (neu5gc), which has been discussed as a virus receptor. human cells cannot synthesize neu5gc due to dysfunction of the cmp-neu5ac hydroxylase (cmah) gene, which converts cmp-neu5ac to cmp-neu5gc. however, exogenous neu5gc from neu5gc-rich dietary sources is able to be metabolically incorporated into surfaces of tissue cells and may be related to enhancement of the infect ...201424829344
comparison between virus shedding and fever duration after treating children with pandemic a h1n1/09 and children with a h3n2 with a neuraminidase inhibitor.shedding of the pandemic virus during an influenza pandemic is thought to persist longer than shedding of influenza viruses during annual influenza seasons, because people have much less immunity against a pandemic influenza. a correlation is thought to exist between the length of virus shedding and the clinical severity of influenza illness.201524832015
the use of plethysmography in determining the severity of lung pathology in a mouse model of minimally lethal influenza virus infection.to characterize the impact on lung function, we assessed plethysmography parameters in a course of infection with mouse-adapted a/pennsylvania/14/2010 (h3n2) influenza virus. several parameters, represented by enhanced pause (penh) and ratio of inspiratory/expiratory time (ti/te), were observed that had early (1-7dpi) and robust changes regardless of virus challenge dose. other parameters, characterized by tidal volume (tv), breathing frequency (freq) and end inspiratory pause (eip), changed lat ...201424837607
protective efficacy of intranasally administered bivalent live influenza vaccine and immunological mechanisms underlying the protection.previously we reported the generation of a new potential live attenuated influenza vaccine (laiv) named siv/606 that expresses h1 and h3 has. we also demonstrated intratracheal vaccination of siv/606 conferred protection against infections with both h1 and h3 swine influenza virus subtypes in pigs. here we vaccinated pigs with siv/606 intranasally, which is a more suitable route for laiv, and evaluated vaccine efficacy. intranasal vaccination of siv/606 induced serum igg antibody responses again ...201424837774
structural basis for histone mimicry and hijacking of host proteins by influenza virus protein ns1.pathogens can interfere with vital biological processes of their host by mimicking host proteins. the ns1 protein of the influenza a h3n2 subtype possesses a histone h3k4-like sequence at its carboxyl terminus and has been reported to use this mimic to hijack host proteins. however, this mimic lacks a free n-terminus that is essential for binding to many known h3k4 readers. here we show that the double chromodomains of chd1 adopt an 'open pocket' to interact with the free n-terminal amine of h3k ...201424853335
safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: a phase i dose escalating study in healthy volunteers.live attenuated influenza vaccine (laiv) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. laivs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (mdvs) containing the surface glycoprotein genes of seasonal influenza strains. two types of mdv lineages have been described, the ann arbor lineages and the a/leningrad/17 and b/ussr/60 lineages. here the safety and immunogenicity of a madin da ...201424858566
[optimization of culture condition for cultivation of influenza virus a on mdck cell].to optimize the cultivation condition of influenza virus a on mdck cells and to improve the separation rate and the inspected effect of influenza virus.201424868970
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