Differential induction of cytotoxicity and apoptosis by influenza virus strains of differing virulence

Two influenza viruses of differing virulence, clone 7a (virulent for humans and ferrets) and A/Fiji (attenuated for both species), induced differential levels of cytotoxicity (as measured by release of lactate dehydrogenase from cells) and apoptosis (as determined by altered nuclear morphology or flow cytometry) in MDCK and U-937 cells. Clone 7a induced more apoptosis and cytotoxicity than A/Fiji, despite the fact that its infectious virus yields were similar to or less than those for A/Fiji. This indicates a greater capacity of clone 7a to induce the two phenomena. Nevertheless the replication process was clearly essential, since UV-irradiated virus induced little or no apoptosis, and apoptosis occurred as a late event post-infection. The possible relevance of these findings to destruction of host cells by influenza virus in vivo is discussed.