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Molecular basis of the structure and function of H1 hemagglutinin of influenza virus.

ABSTRACT: Influenza virus hemagglutinin (HA) contains antigenic sites recognized by the host immune system, cleavage sites cleaved by host proteases, receptor binding sites attaching to sialyl receptors on the target cell, and fusion peptides mediating membrane fusion. Change in an amino acid(s) in these sites may affect the potential of virus infection and spread within and between hosts. Influenza viruses with H1 HA infect birds, pigs and humans and have caused two of the four pandemics in the past 100 years: 1918 pandemic that killed 21-50 million people and 2009 pandemic that caused more than 18,000 deaths. Understanding the relationship between antigenic structure and immune specificity, the receptor binding specificity in virus transmission, how the cleavage site controls pathogenicity, and how the fusion peptide causes membrane fusion for the entry of influenza virus into the host cell should provide information to find more effective ways to prevent and control influenza.

SUBMITTER: Sriwilaijaroen N

PROVIDER: S-EPMC3410141 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Molecular basis of the structure and function of H1 hemagglutinin of influenza virus.

Sriwilaijaroen Nongluk N Suzuki Yasuo Y

Proceedings of the Japan Academy. Series B, Physical and biological sciences 20120101 6

Influenza virus hemagglutinin (HA) contains antigenic sites recognized by the host immune system, cleavage sites cleaved by host proteases, receptor binding sites attaching to sialyl receptors on the target cell, and fusion peptides mediating membrane fusion. Change in an amino acid(s) in these sites may affect the potential of virus infection and spread within and between hosts. Influenza viruses with H1 HA infect birds, pigs and humans and have caused two of the four pandemics in the past 100 ...[more]

PMID: 22728439

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Project description:UnlabelledZoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backbone, differing only by hemagglutinin subtype expressed. Viruses expressing the avian H1, H6, H7, H10, and H15 subtypes were pathogenic in mice and cytopathic in normal human bronchial epithelial cells, in contrast to H2-, H3-, H5-, H9-, H11-, H13-, H14-, and H16-expressing viruses. Mouse pathogenicity was associated with pulmonary macrophage and neutrophil recruitment. These data suggest that avian influenza virus hemagglutinins H1, H6, H7, H10, and H15 contain inherent mammalian virulence factors and likely share a key virulence property of the 1918 virus. Consequently, zoonotic infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals.ImportanceInfluenza viruses from birds can cause outbreaks in humans and may contribute to the development of pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its main surface protein, an H1 subtype hemagglutinin, was identified as a key mammalian virulence factor. In a previous study, a 1918 virus expressing an avian H1 gene was as virulent in mice as the reconstructed 1918 virus. Here, a set of avian influenza viruses was constructed, differing only by hemagglutinin subtype. Viruses with the avian H1, H6, H7, H10, and H15 subtypes caused severe disease in mice and damaged human lung cells. Consequently, infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals, and therefore surveillance for human infections with these subtypes may be important in controlling future outbreaks.

Project description:Serious concern about the worldwide transmission of the Asian H5N1 highly pathogenic (HP) avian influenza (AI) virus by migratory birds surrounds the importance of the AI global surveillance in wild aquatic birds and underscores the requirement for a reliable subtyping method of AI viruses. PCR is advantageous due to its simplicity, lower cross-reactivity, and unlimited reagent supply. Currently, the only available hemagglutinin (HA) subtyping primer set that can subtype H1 through H15 is not fully evaluated and, since it only targets HA1, is unavailable for molecular pathotyping of AI viruses. Our preliminary experiments found that these primer sets were cross-reactive and missed some recent AI viruses. In this study, we developed new primer sets against HA cleavage sites for subtyping H1 to H15 genes and for molecular pathotyping. Our primer sets were subtype specific and detected 99% of previously identified HA genes (115/116, 1949 to March 2006), and the correct amplifications of HA genes were confirmed by sequence analyses of all 115 PCR products. The primer sets successfully subtyped most of the recent AI viruses isolated in Japan (96% [101/105], October 2006 to March 2007). Taken together, our primer sets could efficiently detect HA genes (98% [216/221]) of both previously and recently identified HA genes or of both American (29/29) and Eurasian (187/192) lineages. All 38 H5 and 13 H7 viruses were molecularly pathotyped by sequencing analyses of the HA cleavage site. In contrast, despite efficient detection of previously identified strains (98% [114/116]), the published primer sets exhibited lower specificity and lower detection efficiency against recent AI viruses (80% [84 of 105]). These results indicate that our primers are useful not only for HA subtyping but also for molecular pathotyping of both previous and recent AI viruses. These advancements will enable general diagnostic laboratories to subtype AI viruses for the surveillance in wild aquatic birds.

Dataset Information

Molecular basis of the structure and function of H1 hemagglutinin of influenza virus.

Publications

Molecular basis of the structure and function of H1 hemagglutinin of influenza virus.

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