Hemagglutinin polymorphism as the basis for low- and high-yield phenotypes of swine influenza virus.
Single amino acid substitutions at the rim of the receptor binding site of the hemagglutinin molecule of swine influenza virus markedly influence the replicative capacity of the virus in chicken embryos, Madin-Darby canine kidney cells (MDCK), and swine as well as its antigenic phenotype. Mutants of low-yield (L) phenotype replicate poorly in chicken embryos and produce small plaques in MDCK cells but are highly infective for swine. Such mutants have lysine at position 153 and glycine at position 155 of the hemagglutinin (residues 156 and 158 in the H3 model). High-yield (H) mutants have the converse replicative characteristics and can be antigenically distinguished from L mutants (and from each other) based on their differential reactivity with two monoclonal antibodies, 9C8 and Sa-13. H mutants differ from L mutants in that the H mutants express glutamic acid at either position 153 or 155. L and H mutants act in an allelic fashion in effecting predictable one-step adaptation to different hosts. Selection for replication (e.g., high-yielding) phenotype results in concordant pleiotropic change in antigenic phenotype and in genotype. Conversely, immunoselection leads to change in replicative phenotype. Although the mechanism by which these mutations affect viral replication has not yet been defined, they may reflect differences in the affinity of each mutant for different host receptors.
Kilbourne
E D
ED
Mount Sinai School of Medicine, City University of New York, NY 10029.
Taylor
A H
AH
Whitaker
C W
CW
Sahai
R
R
Caton
A J
AJ
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D006389:Hemagglutinins, Viral / Q000235:genetics*; D009980:Influenza A virus / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D013552:Swine; D014779:Virus Replication
D006389:Hemagglutinins, Viral