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

Caroline M. Coffey, Alexander Sheh, Irene S. Kim, Kartik Chandran, Max L. Nibert, John S.L. Parker

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

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 μ1 protein, encoded by the M2 gene, was sufficient to induce apoptosis in transfected cells. We also found that μ1 localized to lipid droplets, endoplasmic reticulum, and mitochondria in both transfected cells and infected cells. Two small regions encompassing amphipathic α-helices within a carboxyl-terminal portion of μ1 were necessary for efficient induction of apoptosis and association with lipid droplets, endoplasmic reticulum, and mitochondria in transfected cells. Induction of apoptosis by μ1 and its association with lipid droplets and intracellular membranes in transfected cells were abrogated when μ1 was coexpressed with σ3, with which it is known to coassemble. We propose that μ1 plays a direct role in the induction of apoptosis in infected cells and that this property may relate to the capacity of μ1 to associate with intracellular membranes. Moreover, during reovirus infection, association with σ3 may regulate apoptosis induction by μ1.

Original languageEnglish (US)
Pages (from-to)8422-8438
Number of pages17
JournalJournal of virology
Volume80
Issue number17
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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