The
collectins,
lung surfactant proteins A and D (SP-A and
SP-D), contribute to innate host defense against influenza A virus (IAV) in vivo. Although
collectins bind to the
viral hemagglutinin (HA) and inhibit early stages of
viral infection in vitro, they also bind to the
neuraminidase (NA) and inhibit NA activity. We used a variety of NA functional assays, viral strains and recombinant (mutant or wild type)
collectins to characterize the mechanism of NA inhibition. NA inhibition by
SP-D correlates with binding of its
carbohydrate recognition domain (CRD) to oligomannose
oligosaccharides on the
viral hemagglutinin (HA). The effects of
SP-D are additive with
oseltamivir, consistent with differences in mechanism of action. NA inhibition was observed using
fetuin or MDCK cells as a substrate, but not in assays using a soluble
sialic acid analogue.
Collectin multimerization and CRD binding properties are key determinants for NA inhibition.
SP-D had greater NA inhibitory activity than
mannose-binding lectin, which in turn had greater activity than SP-A. The markedly greater NA inhibitory activity of
SP-D compared to SP-A may partly account for the finding that deletion of the
SP-D gene in mice has a greater effect on viral replication in vivo.