MAVS-mediated apoptosis and its inhibition by viral proteins. PLoS One 2009;4(5):e5466
Date
05/01/2009Pubmed ID
19404494Pubmed Central ID
PMC2674933DOI
10.1371/journal.pone.0005466Scopus ID
2-s2.0-84875981860 (requires institutional sign-in at Scopus site) 173 CitationsAbstract
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.
Author List
Lei Y, Moore CB, Liesman RM, O'Connor BP, Bergstralh DT, Chen ZJ, Pickles RJ, Ting JPAuthor
Rachael M. Liesman PhD Associate Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Apoptosis
Base Sequence
Caspases
Cell Line
Cells, Cultured
Endoribonucleases
Host-Pathogen Interactions
Humans
Interferon Regulatory Factor-3
Interferon Type I
Mice
Mice, Knockout
Mitochondria
Models, Biological
NF-kappa B
Protein Structure, Tertiary
RNA, Small Interfering
Sendai virus
Viral Nonstructural Proteins
Viral Proteins
