The importance of influenza viruses as worldwide pathogens in humans, domes
tic animals, and poultry is well recognized. Discerning how influenza virus
es interact with the host at a cellular level is crucial for a better under
standing of viral pathogenesis. Influenza viruses induce apoptosis through
mechanisms involving the interplay of cellular and viral factors that may d
epend on the cell type. However, it is unclear which viral genes induce apo
ptosis. In these studies, we show that the expression of the nonstructural
(NS) gene of influenza A virus is sufficient to induce apoptosis in MDCK an
d HeLa cells. Further studies showed that the multimerization domain of the
NS1 protein but not the effector domain is required for apoptosis. However
, this mutation is not sufficient to inhibit apoptosis using whole virus.