Genetic dimorphism in influenza viruses: Characterization of stably associated hemagglutinin mutants differing in antigenicity and biological properties

Abstract

Influenza virus recombinant X-53 produced for use in the 1976 National Immunization Program for swine influenza comprised 2 types of virions differing in their antigenic, replicative and plaque-forming characteristics. One type, characteristic of X-53 and designated L, was relatively low-yielding in chicken embryos, produced small clear plaques in Madin-Darby dog kidney cells, and was selectively inhibited by heterotypic antibody to the A/sw/Cam/39 strain of swine influenza virus. The other, X-53a or H, was high-yielding in chicken embryos, produced large turbid plaques in dog kidney cells and was not inhibited by concentrations of A/sw/Cam/39 antisera inhibitory to X-53. A/NJ/11/76 (HswN1) virus, from which X-53 was derived, and 5 other swine influenza virus isolates from humans and pigs were dimorphic mixtures of the 2 types of virus. Segregation of the hemagglutinin genes of L and H variants by further recombination demonstrated that their different properties were pleiotropic phenotypes of mutation in the hemagglutinin gene. Under selective conditions suppressive to the L mutant, mutation of cloned L to H virus was observed. This observation, and the apparent ubiquity of the 2 mutants in nature, suggests that this is another example of viral dimorphism, the stable association of 2 allelic mutants. Of special significance is the indication that antigenic variants may be selected by selection for properties other than antigenicity, and therefore may represent mutants with pathogenic effects determined by factors other than lesser modulation by host antibody.