Reovirus outer capsid protein μ1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria

The mechanisms by which reoviruses induce apoptosis have not been fully elucidated. Earlier studies identified the mammalian reovirus S1 and M2 genes as determinants of apoptosis induction. However, no published results have demonstrated the capacities of the proteins encoded by these genes to induce apoptosis, either independently or in combination, in the absence of reovirus infection. Here we report that the mammalian reovirus mu 1 protein, encoded by the M2 gene, was sufficient to induce apoptosis in transfected cells. We also found that mu 1 localized to lipid droplets, endoplasmic reticulum, and mitochondria in both transfected cells and infected cells. Two small regions encompassing amphipathic alpha-helices within a carboxyl-terminal portion of mu 1 were necessary for efficient induction of apoptosis and association with lipid droplets, endoplasmic reticulum, and mitochondria in transfected cells. Induction of apoptosis by mu 1 and its association with lipid droplets and intracellular membranes in transfected cells were abrogated when mu 1 was coexpressed with sigma 3, with which it is known to coassemble. We propose that mu 1 plays a direct role in the induction of apoptosis in infected cells and that this property may relate to the capacity of mu 1 to associate with intracellular membranes. Moreover, during reovirus infection, association with sigma 3 may regulate apoptosis induction by mu 1.