Influenza A viruses lacking sialidase activity can undergo multiple cyclesof replication in cell culture, eggs, or mice

Influenza A viruses possess both hemagglutinin (HA), which is responsible f or binding to the terminal sialic acid of sialyloligosaccharides on the cel l surface, and neuraminidase (NA), which contains sialidase activity that r emoves sialic acid from sialyloligosaccharides. Interplay between HA recept or-binding and NA receptor-destroying sialidase activity appears to be impo rtant for replication of the virus. Previous studies by others have shown t hat influenza A viruses lacking sialidase activity can undergo multiple cyc les of replication if sialidase activity is provided exogenously. To invest igate the sialidase requirement of influenza viruses further, we generated a series of sialidase-deficient mutants. Although their growth was less eff icient than that of the parental NA-dependent virus, these viruses underwen t multiple cycles of replication in cell culture, eggs, and mice. To unders tand the molecular basis of this viral growth adaptation in the absence of sialidase activity, we investigated changes in the HA receptor-binding affi nity of the sialidase-deficient mutants, The results show that mutations ar ound the HA receptor-binding pocket reduce the virus's affinity for cellula r receptors, compensating for the loss of sialidase, Thus, sialidase activi ty is not absolutely required in the influenza A virus life cycle but appea rs to be necessary for efficient virus replication.