PloS one · 2009
MAVS-mediated apoptosis and its inhibition by viral proteins.
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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
Аннотация
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.
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.
Предметные рубрики MeSH
Adaptor Proteins, Signal TransducingAnimalsApoptosisBase SequenceCaspasesCell LineCells, CulturedEndoribonucleasesHost-Pathogen InteractionsHumansInterferon Regulatory Factor-3Interferon Type IMiceMice, KnockoutMitochondriaModels, BiologicalNF-kappa BProtein Structure, TertiaryRNA, Small InterferingRNA-Dependent RNA PolymeraseSendai virusViral Nonstructural ProteinsViral Proteins