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eLife: Influenza A virus surface proteins are organized to help penetrate host mucus

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  • eLife: Influenza A virus surface proteins are organized to help penetrate host mucus

    Influenza A virus surface proteins are organized to help penetrate host mucus

    Michael D Vahey

    ,
    • University of California, Berkeley, United States;
    • Lawrence Berkeley National Laboratory, United States;
    • Chan Zuckerberg Biohub, United States

    Abstract

    Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating a spatial organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus?s conflicting needs to both penetrate mucus and stably attach to the underlying cells, potentially contributing to the prevalence of the filamentous phenotype in clinical isolates of IAV.

    full article
    By distributing receptor-binding and receptor-destroying proteins asymmetrically on their surface, filamentous influenza A virus particles create a Brownian ratchet that facilitates their passage through mucus.








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