CONGLUTININ ACTS AS AN OPSONIN FOR INFLUENZA-A VIRUSES

Since the 1940's, non-Ig inhibitors of influenza A virus (IAV) hemaggl utination activity and infectivity have been recognized in mammalian s era. Recently, the heat labile (beta) inhibitor of this type was ident ified by indirect methods as the lectin, conglutinin. In support of th is hypothesis, we found that purified conglutinin strongly inhibited h emagglutination activity and infectivity of IAV. By using IAV strains with specific variations in glycosylation of the hemagglutinin molecul e, we showed these effects to be mediated by binding of conglutinin to high mannose carbohydrate attachments on the viral hemagglutinin. Thr ough the same mechanism conglutinin caused aggregation of IAV particle s. Human neutrophils produce hydrogen peroxide upon exposure to IAV. A lso, after a brief period of exposure to IAV, neutrophils exhibit depr essed responsiveness (deactivation) upon exposure to other stimuli (e. g., chemotactic peptides). These phenomena may be related to the in vi vo inflammatory response during IAV infection, and to the propensity o f IAV-infected subjects to suffer bacterial superinfection. Pre-incuba tion of IAV with conglutinin markedly potentiated human neutrophil hyd rogen peroxide production in response to the virus. This effect correl ated with the ability of conglutinin to aggregate the virus. IAV treat ed with conglutinin also caused significantly less neutrophil deactiva tion than did the unopsonized virus. These enhancements of neutrophil respiratory burst responses by conglutinin were again mediated by bind ing of the lectin to viral carbohydrates. The mammalian C-type lectin family includes conglutinin, mannose-binding protein, and surfactant p roteins A and D. These lectins may be important constituents of the in itial host response to IAV, by inhibiting IAV infectivity directly, ca using viral aggregation, and acting as opsonins to enhance phagocyte r esponses to the virus.