Murine coronavirus-induced apoptosis in 17Cl-1 cells involves a mitochondria-mediated pathway and its downstream caspase-8 activation and bid cleavage

Chun Jen Chen, Shinji Makino

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Mouse hepatitis virus (MHV) infection in murine 17Cl-1 cells results in apoptotic cell death. Inhibition of MHV-induced apoptosis by the pancaspase inhibitor Z-VAD-FMK promoted virus production late in infection, indicating that apoptosis could be a host response to limit the production of viral progeny. Activation of the mitochondria-mediated apoptotic pathway was indicated by the activation of caspase-9 and delay of apoptosis by Bcl-2 overexpression. Analyses of the subcellular distribution of cytochrome c, procaspase-9, and Apaf-1 suggested an aberrant apoptosome formation in the vicinity of the mitochondria, which could be a cell type-specific event. An increase in the amount of Fas (APO-1/CD95), caspase-8 activation, caspase-8-mediated Bid cleavage, and subsequent translocation of truncated Bid to mitochondria, all of which relate to the Fas-mediated pathway, also occurred in MHV-infected 17Cl-1 cells, whereas the formation of the death-inducing signaling complex, a direct indication of the activation of Fas-mediated pathway, was undetectable. Caspase-8 and Bid activation appeared to be downstream of mitochondria, because Bcl-2 overexpression suppressed both events, suggesting that infected 17Cl-1 cells might have activated a receptor-mediated "type II" signaling pathway, in which primary and low levels of receptor-mediated pathway activation lead to the activation of the mitochondria-mediated pathway. All our data indicate that a mitochondria-mediated pathway played a major regulatory role in apoptosis in MHV-infected 17Cl-1 cells.

Original languageEnglish (US)
Pages (from-to)321-332
Number of pages12
JournalVirology
Volume302
Issue number2
DOIs
StatePublished - 2002

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Coronavirus
Caspase 8
Murine hepatitis virus
Mitochondria
Apoptosis
Caspase 9
Death Domain Receptor Signaling Adaptor Proteins
Apoptosomes
Virus Diseases
Cytochromes c
Cell Death
Viruses
Infection

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

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title = "Murine coronavirus-induced apoptosis in 17Cl-1 cells involves a mitochondria-mediated pathway and its downstream caspase-8 activation and bid cleavage",
abstract = "Mouse hepatitis virus (MHV) infection in murine 17Cl-1 cells results in apoptotic cell death. Inhibition of MHV-induced apoptosis by the pancaspase inhibitor Z-VAD-FMK promoted virus production late in infection, indicating that apoptosis could be a host response to limit the production of viral progeny. Activation of the mitochondria-mediated apoptotic pathway was indicated by the activation of caspase-9 and delay of apoptosis by Bcl-2 overexpression. Analyses of the subcellular distribution of cytochrome c, procaspase-9, and Apaf-1 suggested an aberrant apoptosome formation in the vicinity of the mitochondria, which could be a cell type-specific event. An increase in the amount of Fas (APO-1/CD95), caspase-8 activation, caspase-8-mediated Bid cleavage, and subsequent translocation of truncated Bid to mitochondria, all of which relate to the Fas-mediated pathway, also occurred in MHV-infected 17Cl-1 cells, whereas the formation of the death-inducing signaling complex, a direct indication of the activation of Fas-mediated pathway, was undetectable. Caspase-8 and Bid activation appeared to be downstream of mitochondria, because Bcl-2 overexpression suppressed both events, suggesting that infected 17Cl-1 cells might have activated a receptor-mediated {"}type II{"} signaling pathway, in which primary and low levels of receptor-mediated pathway activation lead to the activation of the mitochondria-mediated pathway. All our data indicate that a mitochondria-mediated pathway played a major regulatory role in apoptosis in MHV-infected 17Cl-1 cells.",
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N2 - Mouse hepatitis virus (MHV) infection in murine 17Cl-1 cells results in apoptotic cell death. Inhibition of MHV-induced apoptosis by the pancaspase inhibitor Z-VAD-FMK promoted virus production late in infection, indicating that apoptosis could be a host response to limit the production of viral progeny. Activation of the mitochondria-mediated apoptotic pathway was indicated by the activation of caspase-9 and delay of apoptosis by Bcl-2 overexpression. Analyses of the subcellular distribution of cytochrome c, procaspase-9, and Apaf-1 suggested an aberrant apoptosome formation in the vicinity of the mitochondria, which could be a cell type-specific event. An increase in the amount of Fas (APO-1/CD95), caspase-8 activation, caspase-8-mediated Bid cleavage, and subsequent translocation of truncated Bid to mitochondria, all of which relate to the Fas-mediated pathway, also occurred in MHV-infected 17Cl-1 cells, whereas the formation of the death-inducing signaling complex, a direct indication of the activation of Fas-mediated pathway, was undetectable. Caspase-8 and Bid activation appeared to be downstream of mitochondria, because Bcl-2 overexpression suppressed both events, suggesting that infected 17Cl-1 cells might have activated a receptor-mediated "type II" signaling pathway, in which primary and low levels of receptor-mediated pathway activation lead to the activation of the mitochondria-mediated pathway. All our data indicate that a mitochondria-mediated pathway played a major regulatory role in apoptosis in MHV-infected 17Cl-1 cells.

AB - Mouse hepatitis virus (MHV) infection in murine 17Cl-1 cells results in apoptotic cell death. Inhibition of MHV-induced apoptosis by the pancaspase inhibitor Z-VAD-FMK promoted virus production late in infection, indicating that apoptosis could be a host response to limit the production of viral progeny. Activation of the mitochondria-mediated apoptotic pathway was indicated by the activation of caspase-9 and delay of apoptosis by Bcl-2 overexpression. Analyses of the subcellular distribution of cytochrome c, procaspase-9, and Apaf-1 suggested an aberrant apoptosome formation in the vicinity of the mitochondria, which could be a cell type-specific event. An increase in the amount of Fas (APO-1/CD95), caspase-8 activation, caspase-8-mediated Bid cleavage, and subsequent translocation of truncated Bid to mitochondria, all of which relate to the Fas-mediated pathway, also occurred in MHV-infected 17Cl-1 cells, whereas the formation of the death-inducing signaling complex, a direct indication of the activation of Fas-mediated pathway, was undetectable. Caspase-8 and Bid activation appeared to be downstream of mitochondria, because Bcl-2 overexpression suppressed both events, suggesting that infected 17Cl-1 cells might have activated a receptor-mediated "type II" signaling pathway, in which primary and low levels of receptor-mediated pathway activation lead to the activation of the mitochondria-mediated pathway. All our data indicate that a mitochondria-mediated pathway played a major regulatory role in apoptosis in MHV-infected 17Cl-1 cells.

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