Two evolutionary strategies of influenza viruses to escape host non-specific inhibitors: alteration of hemagglutinin or neuraminidase specificity.
The porcine serum inhibitor alpha 2-macroglobulin prevents influenza virus from entering host cells by competing for the SA alpha 2, 6Gal-binding site of the hemagglutinin (HA). We studied a series of inhibitor-sensitive and inhibitor-resistant human and porcine influenza virus isolates of the H3N2 subtype, all of which contained HAs, which initially bound only to SA alpha 2, 6Gal oligosaccharides. When their neuraminidase was inhibited, the naturally resistant viruses, as a result of no longer being able to elute from the inhibitor, became sensitive. Evidently it is the neuraminidase which enabled these viruses to grow in hosts which possess the inhibitor. Escape-mutants selected under laboratory conditions in the presence of porcine serum became inhibitor-resistant by two alternative mechanisms: they changed either their HA-specificity or their neuraminidase-specificity. The study thus disclosed two evolutionary strategies for acquiring resistance to a host neuraminidase-sensitive inhibitor: (i) acquisition of an HA able to bind to oligosaccharides not present on the inhibitor; or (ii) acquisition of a neuraminidase able to cleave the oligosaccharide bound by the HA.
Gimsa
U
U
Deutsches RheumaForschungsZentrum Berlin, Germany.
Grötzinger
I
I
Gimsa
J
J
D000818:Animals; D002642:Chick Embryo; D018397:Equidae / Q000097:blood; D004912:Erythrocytes / Q000276:immunology; D019143:Evolution, Molecular; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D009439:Neuraminidase / Q000276:immunology*; D009500:Neutralization Tests; D013379:Substrate Specificity; D013552:Swine / Q000821:virology
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009439:Neuraminidase