Article

Inhibition of influenza viral neuraminidase activity by collectins.

Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Archives of Virology (impact factor: 2.11). 02/2007; 152(9):1731-42. DOI:10.1007/s00705-007-0983-4 pp.1731-42
Source: PubMed

ABSTRACT 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.

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Keywords

carbohydrate recognition domain
 
collectins bind
 
CRD binding properties
 
greater effect
 
innate host defense
 
lung surfactant proteins
 
mannose-binding lectin
 
markedly greater NA inhibitory activity
 
NA activity
 
NA functional assays
 
NA inhibition
 
oligomannose oligosaccharides
 
soluble sialic acid analogue
 
SP-D correlates
 
SP-D gene
 
viral hemagglutinin
 
viral infection
 
viral replication
 
viral strains
 
wild type