Human annexin A6 interacts with influenza A virus M2 protein and negatively modulates infection.

Abstract : The influenza A virus M2 ion channel protein has the longest cytoplasmic tail (CT) among the three viral envelope proteins and is well conserved between different viral strains. It is accessible to the host cellular machinery after fusion with the endosomal membrane and during the trafficking, assembly and budding processes. We hypothesized that identification of host cellular interactants of the M2 CT could help to better understand the molecular mechanisms regulating the M2-dependent stages of the virus life cycle. Using yeast two-hybrid screening with M2 CT as bait, a novel interaction with the human annexin A6 (AnxA6) protein was identified and their physical interaction was confirmed by co-immunoprecipitation assay and co-localization study on virus infected human cells. We found that siRNA-mediated knockdown of AnxA6 expression significantly increased the virus production, while its overexpression could reduce the titer of virus progeny, suggesting a negative regulatory role for AnxA6 during influenza A virus infection. Further characterization revealed that AnxA6 depletion or overexpression had no effect on the early stages of virus life cycle and viral RNA replication, but impaired the release of progeny virus, as suggested by the delayed or defective budding events observed at the plasma membrane of virus infected cells, revealed by transmission electron microscopy. Collectively, this work identifies AnxA6 as a novel cellular regulator that targets and impairs the virus budding and release stages of the influenza A virus life cycle.
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Submitted on : Monday, November 28, 2011 - 7:13:10 AM
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Huailiang Ma, François Kien, Maxime Manière, Yang Zhang, Nadège Lagarde, et al.. Human annexin A6 interacts with influenza A virus M2 protein and negatively modulates infection.. Journal of Virology, American Society for Microbiology, 2011, epub ahead of print. ⟨10.1128/JVI.06003-11⟩. ⟨pasteur-00645399⟩

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