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

58 Citations (Scopus)

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 2006
Externally publishedYes

Fingerprint

Reoviridae
Capsid Proteins
coat proteins
Endoplasmic Reticulum
endoplasmic reticulum
droplets
Mitochondria
mitochondria
apoptosis
Apoptosis
lipids
Reoviridae Infections
Intracellular Membranes
cells
Mammalian Orthoreovirus
genes
Lipid Droplets
infection
Genes
cell membranes

ASJC Scopus subject areas

  • Immunology

Cite this

Reovirus outer capsid protein μ1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria. / Coffey, Caroline M.; Sheh, Alexander; Kim, Irene S.; Chandran, Kartik; Nibert, Max L.; Parker, John S L.

In: Journal of Virology, Vol. 80, No. 17, 09.2006, p. 8422-8438.

Research output: Contribution to journalArticle

Coffey, Caroline M. ; Sheh, Alexander ; Kim, Irene S. ; Chandran, Kartik ; Nibert, Max L. ; Parker, John S L. / Reovirus outer capsid protein μ1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria. In: Journal of Virology. 2006 ; Vol. 80, No. 17. pp. 8422-8438.
@article{3636d14c3c6841f9a9093e8b0d7c5b60,
title = "Reovirus outer capsid protein μ1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria",
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.",
author = "Coffey, {Caroline M.} and Alexander Sheh and Kim, {Irene S.} and Kartik Chandran and Nibert, {Max L.} and Parker, {John S L}",
year = "2006",
month = "9",
doi = "10.1128/JVI.02601-05",
language = "English (US)",
volume = "80",
pages = "8422--8438",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "17",

}

TY - JOUR

T1 - Reovirus outer capsid protein μ1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and mitochondria

AU - Coffey, Caroline M.

AU - Sheh, Alexander

AU - Kim, Irene S.

AU - Chandran, Kartik

AU - Nibert, Max L.

AU - Parker, John S L

PY - 2006/9

Y1 - 2006/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33748641937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748641937&partnerID=8YFLogxK

U2 - 10.1128/JVI.02601-05

DO - 10.1128/JVI.02601-05

M3 - Article

C2 - 16912293

AN - SCOPUS:33748641937

VL - 80

SP - 8422

EP - 8438

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 17

ER -