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J Virol. 2014 Jul 16. pii: JVI.01405-14. [Epub ahead of print]
Annexin V incorporated into influenza virus particles inhibits interferon-γ signaling and promotes viral replication.
Berri F1, Haffar G1, Ba L? V1, Sadewasser A2, Paki K2, Lina B1, Wolff T2, Riteau B3.
Author information
Abstract
During the budding process, influenza A viruses (IAVs) incorporate multiple host cell membrane proteins. However, for most of them, their significance in viral morphogenesis and infectivity remains unknown. Here we demonstrate that the expression of annexin V (A5) is up-regulated at the cell surface upon IAV infection and that a substantial proportion of the protein is present in lipid rafts, the site of virus budding. Western blotting and immunogold analysis of highly purified IAV particles showed the presence of A5 in the virion. Significantly, interferon-γ (IFN-γ) induced stat-phosphorylation and IFN-γ-induced protein 10 kDa (IP-10) production in macrophage-derived THP-1 cells was inhibited by purified IAV particles. Disruption of the IFN-γ signaling pathway was A5 dependent as down-regulation of its expression or its blockage reversed the inhibition and resulted in decreased viral replication, in vitro. The functional significance of these results was also observed in vivo. Thus, IAVs can subvert the IFN-γ antiviral immune response by incorporating A5 in their envelope during the budding process.
IMPORTANCE:
Many enveloped viruses including influenza A viruses bud from the plasma membrane of their host cell and incorporate cellular surface proteins into viral particles. However, for the vast majority of these proteins, only the observation of their incorporation has been reported. In this manuscript, we demonstrated that the host protein annexin 5 is specifically incorporated into influenza virus particles during the budding process. Importantly, we showed that packaged annexin 5 counteracted the antiviral activity of interferon-gamma in vitro and in vivo. Thus, these results showed that Annexin 5 incorporated in the viral envelope of influenza viruses allow viral escape from immune surveillance. Understanding the role of host incorporated protein into virions may reveal how enveloped RNA viruses hijack the host cell machinery for their own purposes.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25031344
[PubMed - as supplied by publisher]
Annexin V incorporated into influenza virus particles inhibits interferon-γ signaling and promotes viral replication.
Berri F1, Haffar G1, Ba L? V1, Sadewasser A2, Paki K2, Lina B1, Wolff T2, Riteau B3.
Author information
Abstract
During the budding process, influenza A viruses (IAVs) incorporate multiple host cell membrane proteins. However, for most of them, their significance in viral morphogenesis and infectivity remains unknown. Here we demonstrate that the expression of annexin V (A5) is up-regulated at the cell surface upon IAV infection and that a substantial proportion of the protein is present in lipid rafts, the site of virus budding. Western blotting and immunogold analysis of highly purified IAV particles showed the presence of A5 in the virion. Significantly, interferon-γ (IFN-γ) induced stat-phosphorylation and IFN-γ-induced protein 10 kDa (IP-10) production in macrophage-derived THP-1 cells was inhibited by purified IAV particles. Disruption of the IFN-γ signaling pathway was A5 dependent as down-regulation of its expression or its blockage reversed the inhibition and resulted in decreased viral replication, in vitro. The functional significance of these results was also observed in vivo. Thus, IAVs can subvert the IFN-γ antiviral immune response by incorporating A5 in their envelope during the budding process.
IMPORTANCE:
Many enveloped viruses including influenza A viruses bud from the plasma membrane of their host cell and incorporate cellular surface proteins into viral particles. However, for the vast majority of these proteins, only the observation of their incorporation has been reported. In this manuscript, we demonstrated that the host protein annexin 5 is specifically incorporated into influenza virus particles during the budding process. Importantly, we showed that packaged annexin 5 counteracted the antiviral activity of interferon-gamma in vitro and in vivo. Thus, these results showed that Annexin 5 incorporated in the viral envelope of influenza viruses allow viral escape from immune surveillance. Understanding the role of host incorporated protein into virions may reveal how enveloped RNA viruses hijack the host cell machinery for their own purposes.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25031344
[PubMed - as supplied by publisher]
