Reovirus Outer Capsid Protein μ1 Induces Apoptosis and Associates with Lipid Droplets, Endoplasmic Reticulum, and Mitochondria
- 1 September 2006
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 80 (17), 8422-8438
- https://doi.org/10.1128/jvi.02601-05
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 whenμ 1 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 byμ 1.Keywords
This publication has 62 references indexed in Scilit:
- Sequences of avian reovirus M1, M2 and M3 genes and predicted structure/function of the encoded μ proteinsVirus Research, 2006
- JAM-A-Independent, Antibody-Mediated Uptake of Reovirus into Cells Leads to ApoptosisJournal of Virology, 2006
- Influenza Virus PB1-F2 Protein Induces Cell Death through Mitochondrial ANT3 and VDAC1PLoS Pathogens, 2005
- Nonstructural Protein σ1s Is a Determinant of Reovirus Virulence and Influences the Kinetics and Severity of Apoptosis Induction in the Heart and Central Nervous SystemJournal of Virology, 2005
- Mechanisms of Reovirus-Induced Cell Death and Tissue Injury: Role of Apoptosis and Virus-Induced Perturbation of Host-Cell Signaling and Transcription Factor ActivationViral Immunology, 2005
- Cell DeathCell, 2004
- Avian Reoviruses Cause Apoptosis in Cultured Cells: Viral Uncoating, but Not Viral Gene Expression, Is Required for Apoptosis InductionJournal of Virology, 2002
- Reovirus Infection Activates JNK and the JNK-Dependent Transcription Factor c-JunJournal of Virology, 2001
- Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cellsEuropean Journal of Clinical Investigation, 1999
- Emerging roles of caspase-3 in apoptosisCell Death & Differentiation, 1999