Toxicity, Pathogenicity and Antigenicity of Inhibitor-Sensitive and Nonsensitive Substrains of Influenza A2 Isolates

Abstract

Inhibitor nonsensitive (S-) and inhibitor sensitive (S+) substrains were recovered from a series of apparently sensitive A₂ influenza viruses. The selection of S- substrains was facilitated by an initial passage in de-embryonated eggs of high concentrations of the parent strains in the presence of horse serum. Depending on the ratio of S- to S+ particles originally present in the mixed population, S- progeny appeared either immediately in the de-embryonated egg fluids or on a further passage in ovo of de-embryonated egg fluids in which hemagglutinins were nondetectable or of very low titers. Pure lines of S- virus were then established by passage of the S- progeny at limiting dilutions beyond the 50% infectivity level in the absence of horse serum. Pure populations of S+ particles were obtained by similar passage without horse serum at limiting dilutions of the parent virus. It was found that S- particles were slightly more toxic than S+ particles when tested in mice by the intravenous or intracerebral routes. However, neither appeared pathogenic for the same host when given by the respiratory route. Similarly, no differences could be demonstrated with regard to their lethality for the chick embryo for both of them caused death to the same degree. On examination of the two kinds of substrains by the strain-specific complement-fixation test, it became apparent that they could be distinguished serologically. S+ particles recovered from a given A₂ virus appeared to be antigenically identical with S+ particles recovered from other A₂ viruses of the same year, but distinct from S- particles and vice versa. Avidity for antibody played no role in this phenomenon. However, it was noted that on primary immunization, S- particles were capable of provoking more substantial homologous antibody titers than S+ particles. The implication of these findings are discussed.