Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin.
The nature of the beta inhibitor in guinea-pig serum and its mechanism of neutralization of influenza virus have been investigated. This inhibitor was shown to be a mannose-binding lectin serologically related to human serum mannose-binding protein. Ca(2+)-dependent binding of the guinea-pig lectin to influenza virus or to mannan could be detected with polyclonal or monoclonal antibodies against human mannose-binding protein in an ELISA. Furthermore, the monoclonal antibody inhibited both the haemagglutination-inhibiting and virus-neutralizing activities of the guinea-pig lectin. The lectin was active against influenza viruses of both type A and type B. In haemagglutination inhibition it acts independently of complement, apparently by sterically hindering access to the receptor-binding site on the viral haemagglutinin through binding of the lectin to carbohydrate side-chains in the vicinity of this site. Neutralization by the lectin, however, was shown to require activation of the classical complement pathway. To our knowledge, the neutralization of influenza virus by a serum lectin plus complement represents a previously unrecognized mechanism of complement-dependent viral inactivation that may be important in first-line host defence against a variety of enveloped viruses.
Anders
E M
EM
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Hartley
C A
CA
Reading
P C
PC
Ezekowitz
R A
RA
D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D006168:Guinea Pigs; D006385:Hemagglutination Inhibition Tests; D037102:Lectins / Q000097:blood / Q000276:immunology*; D008358:Mannose / Q000276:immunology*; D037241:Mannose-Binding Lectins; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000276:immunology*
D002352:Carrier Proteins; D037102:Lectins; D037241:Mannose-Binding Lectins; D008358:Mannose