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. © 2009 Lei et al.
CITATION STYLE
Lei, Y., Moore, C. B., Liesman, R. M., O’Connor, B. P., Bergstralh, D. T., Chen, Z. J., … Ting, J. P. Y. (2013). MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins. PLoS ONE, 4(2). https://doi.org/10.1371/journal.pone.0005466
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