Bovine and mouse serum beta inhibitors of influenza A viruses are mannose-binding lectins.
Normal bovine and mouse sera contain a component, termed beta inhibitor, that inhibits the infectivity and hemagglutinating activity of influenza A viruses of the H1 and H3 subtypes. To investigate the nature of the interaction of beta inhibitors with influenza A viruses we isolated a mutant of the virus Mem71H-BelN (H3N1) that could grow in the presence of bovine serum. The mutant virus was resistant to hemagglutination inhibition by mouse serum as well as by bovine serum and had undergone changes in the receptor-binding and the antigenic properties of its hemagglutinin (HA) molecule. Sequence analysis of the HA genes of parent and mutant viruses revealed a single nucleotide change in the mutant, resulting in the substitution Thr----Asn at residue 167 of the HA1 chain of HA. This change leads to loss of the potential glycosylation site Asn-165-Val-166-Thr-167 at the tip of the HA spike, which in viruses of the H3 subtype is known to bear a high-mannose (type II) carbohydrate side chain N-linked to Asn-165. The association of beta inhibitor resistance with loss of this carbohydrate side chain suggested that beta inhibitors may be lectins. In support of this hypothesis, treatment of the beta inhibitor-sensitive parent virus Mem71H-BelN with periodate converted it to the resistant state. Furthermore, the inhibitory activity of both bovine and mouse sera for the parental virus was abrogated by D-mannose. We conclude that the beta inhibitors in bovine and mouse sera are mannose-binding lectins that inhibit hemagglutination and neutralize virus infectivity by binding to carbohydrate at the tip of the HA spike, blocking access of cell-surface receptors to the receptor-binding site on HA.
Anders
E M
EM
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Hartley
C A
CA
Jackson
D C
DC
D000818:Animals; D002352:Carrier Proteins / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D002417:Cattle; D004352:Drug Resistance, Microbial / Q000235:genetics; D005814:Genes, Viral; D006384:Hemagglutination; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D037102:Lectins / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D008358:Mannose / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D037241:Mannose-Binding Lectins; D051379:Mice; D009154:Mutation; D010504:Periodic Acid / Q000494:pharmacology; D017680:Potassium Compounds; D015678:Viral Structural Proteins / Q000235:genetics
D002352:Carrier Proteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D037102:Lectins; D037241:Mannose-Binding Lectins; D017680:Potassium Compounds; D015678:Viral Structural Proteins; D010504:Periodic Acid; D008358:Mannose; C037192:potassium periodate