MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins

Yu Lei, Chris B. Moore, Rachael M. Liesman, Brian P. O'Connor, Daniel T. Bergstralh, Zhijian J. Chen, Raymond J. Pickles, Jenny P Y Ting

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Background: Host responses to viral infection include both immune activation and programmed cell death. The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. Principal Findings: We show that MAVS causes apoptosis independent of its function in initiating IFN-I production. MAVS-induced cell death requires mitochondrial localization, is caspase dependent, and displays hallmarks of apoptosis. Furthermore, MAVS-/- fibroblasts are resistant to Sendai virus-induced apoptosis. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. Significance: This study describes a novel role for MAVS in controlling viral infections through the induction of apoptosis, and identifies viral proteins which inhibit this host response.

Original languageEnglish (US)
Article numbere5466
JournalPLoS One
Volume4
Issue number2
StatePublished - 2009

Fingerprint

viral proteins
Viral Proteins
apoptosis
Apoptosis
Virus Diseases
Viruses
Cell death
Cell Death
Immune Evasion
Sendai virus
Severe Acute Respiratory Syndrome
Interferon Type I
infection
immune evasion
Fibroblasts
Caspases
Hepatitis C virus
Hepacivirus
caspases
Antiviral Agents

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lei, Y., Moore, C. B., Liesman, R. M., O'Connor, B. P., Bergstralh, D. T., Chen, Z. J., ... Ting, J. P. Y. (2009). MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins. PLoS One, 4(2), [e5466].

MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins. / Lei, Yu; Moore, Chris B.; Liesman, Rachael M.; O'Connor, Brian P.; Bergstralh, Daniel T.; Chen, Zhijian J.; Pickles, Raymond J.; Ting, Jenny P Y.

In: PLoS One, Vol. 4, No. 2, e5466, 2009.

Research output: Contribution to journalArticle

Lei, Y, Moore, CB, Liesman, RM, O'Connor, BP, Bergstralh, DT, Chen, ZJ, Pickles, RJ & Ting, JPY 2009, 'MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins', PLoS One, vol. 4, no. 2, e5466.
Lei Y, Moore CB, Liesman RM, O'Connor BP, Bergstralh DT, Chen ZJ et al. MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins. PLoS One. 2009;4(2). e5466.
Lei, Yu ; Moore, Chris B. ; Liesman, Rachael M. ; O'Connor, Brian P. ; Bergstralh, Daniel T. ; Chen, Zhijian J. ; Pickles, Raymond J. ; Ting, Jenny P Y. / MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins. In: PLoS One. 2009 ; Vol. 4, No. 2.
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