The influence of defective-interfering particles of the PR-8 strain of influenza A virus on the pathogenesis of pulmonary infection in mice

Abstract

Homologous autointerference mediated by defective-interfering (DI) particles was first described with the PR-8 strain of influenza virus. However, little is actually known about the influence of DI particles of influenza virus on the pathogenesis of pulmonary infection. The present studies were designed to determine (1) the requirements for successful autointerference in vivo with DI particle-enriched PR-8 influenza virus and (2) the effects of DI particle-enriched virus on the development and progression of otherwise lethal pulmonary infection in mice. PR-8 influenza virus passaged in chicken eggs, but not that passaged in Madin-Darby bovine kidney cells, and enriched in DI particles markedly attenuated pulmonary infection in seven-week-old Swiss and four-week-old C57B16/Cr mice but not in three- to four-week-old Swiss mice. In addition, replication of influenza virus, straining of viral antigen, and numbers of infiltrates in lungs of mice infected with DI particle-enriched influenza virus were reduced in comparison with values in mice infected with comparable amounts of wild-type influenza virus. The protection mediated by DI particle-enriched virus appeared to be related to augmented humoral immune responses in infected mice rather than to autointerference with replication of wild-type virus.