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Viruses 2019, 11(4), 346; https://doi.org/10.3390/v11040346

Influenza Hemagglutinin and Neuraminidase: Yin–Yang Proteins Coevolving to Thwart Immunity

Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA
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Received: 19 March 2019 / Revised: 11 April 2019 / Accepted: 13 April 2019 / Published: 16 April 2019
(This article belongs to the Special Issue What’s New with Flu?)
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Abstract

Influenza A virions possess two surface glycoproteins—the hemagglutinin (HA) and neuraminidase (NA)—which exert opposite functions. HA attaches virions to cells by binding to terminal sialic acid residues on glycoproteins/glycolipids to initiate the infectious cycle, while NA cleaves terminal sialic acids, releasing virions to complete the infectious cycle. Antibodies specific for HA or NA can protect experimental animals from IAV pathogenesis and drive antigenic variation in their target epitopes that impairs vaccine effectiveness in humans. Here, we review progress in understanding HA/NA co-evolution as each acquires epistatic mutations to restore viral fitness to mutants selected in the other protein by host innate or adaptive immune pressure. We also discuss recent exciting findings that antibodies to HA can function in vivo by blocking NA enzyme activity to prevent nascent virion release and enhance Fc receptor-based activation of innate immune cells. View Full-Text
Keywords: Influenza A virus; hemagglutinin; neuraminidase; viral evolution; antigenic drift Influenza A virus; hemagglutinin; neuraminidase; viral evolution; antigenic drift
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Kosik, I.; Yewdell, J.W. Influenza Hemagglutinin and Neuraminidase: Yin–Yang Proteins Coevolving to Thwart Immunity. Viruses 2019, 11, 346.

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