Influenza virus infection of desialylated cells

Sialic acid has long been considered to be the sole receptor for influenza virus. The viral hemagglutinin (HA) is known to bind cell surface sialic ac id, and sialic acids on viral glycoproteins are cleaved by the viral neuram inidase (NA) to promote efficient release of progeny virus particles. Howev er, NWS-Mvi, a mutant virus completely lacking NA, grows well in MDCK cells continuously treated with exogenous neuraminidase (sialidase), Exogenous s ialidase quantitatively releases all sialic acids from purified glycoprotei ns and glycolipids of MDCK cells and efficiently removes surface sialic aci d from intact cells, Binding of NWS-Mvi and parent influenza viruses to MDC K cells is indistinguishable, and is only partially reduced by sialidase tr eatment of the cells, Both mutant and wild-type viruses enter enzymatically desialylated cells and initiate transcription. The ability of influenza A reassortant viruses to infect desialylated cells is shared by recent H3N2 c linical isolates, suggesting that this may be a general property of influen za A viruses. We propose that influenza virus infection can result from sia lic acid-independent receptors, either directly or in a multistage process. When sialic acid is present, it may act to enhance virus binding to the ce ll surface to increase interaction with secondary receptors to mediate entr y. Understanding virus entry will be critical to further efforts in infecti on control and prevention.