Adaptation of influenza A viruses to cells expressing low levels of sialicacid leads to loss of neuraminidase activity

Influenza A viruses possess two virion surface proteins, hemagglutinin (HA) and neuraminidase (NA). The HA binds to sialyloligosaccharide viral recept ors, while the NA removes sialic acids from the host cell and viral sialylo ligosaccarides. Alterations of the HA occur during adaptation of influenza viruses to new host species, as in the 1957 and 1968 influenza pandemics. T o gain a better understanding of the contributions of the HA and possibly t he NA to this process, we generated cell lines expressing reduced levels of the influenza virus receptor determinant, sialic acid, by selecting Madin- Darby canine kidney cells resistant to a lectin specific for sialic acid li nked to galactose by alpha (2-3) or alpha (2-6) linkages, One of these cell lines had less than 1/10 as much N-acetylneuraminic acid as its parent cel l line. When serially passaged in this cell line, human H3N2 viruses lost s ialidase activity due to a large internal deletion in the NA gene, without alteration of the HA gene. These findings indicate that NA mutations can co ntribute to the adaptation of influenza A virus to new host environments an d hence may play a role in the transmission of virus across species.