Differential interaction of virulent and attenuated influenza virus strains with ferret alveolar macrophages: possible role in pathogenicity.

The ferret provides a unique model for the study of human influenza. The interaction between alveolar macrophages and virus strains with different levels of virulence was examined in vitro. The greater virulence of wild-type A strains over type B and C viruses was reflected in the higher production of infectious virus progeny and subsequent cytopathology, even though the expression of viral antigens was equivalent for all strains tested. These included A/Ann Arbor/6/60 (H2N2) and A/Rochester/1/82 (H3N2), B/Hong Kong/72, and C/Ann Arbor/1/50. The attenuated cold-adapted and temperature-sensitive variant of A/Ann Arbor/6/60 behaved like its parent except that a longer period was needed to reach peak viral release. In contrast, the avirulent host-range reassortant CR-43-3 did not productively replicate, though viral antigen expression was comparable to that of the other strains. Type C virus infected few cells and these continued to release low virus levels in the absence of detectable cytopathology. The results suggest that the ability of certain strains to infect and replicate in alveolar macrophages can be correlated to their in vivo virulence and may play a role in determining the course of viral pathogenesis.