MAVS-mediated apoptosis and its inhibition by viral proteins
- PMID: 19404494
- PMCID: PMC2674933
- DOI: 10.1371/journal.pone.0005466
MAVS-mediated apoptosis and its inhibition by viral proteins
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.
Conflict of interest statement
Figures
Similar articles
-
The MAVS Immune Recognition Pathway in Viral Infection and Sepsis.Antioxid Redox Signal. 2021 Dec;35(16):1376-1392. doi: 10.1089/ars.2021.0167. Epub 2021 Sep 28. Antioxid Redox Signal. 2021. PMID: 34348482 Free PMC article. Review.
-
Dengue Virus Subverts Host Innate Immunity by Targeting Adaptor Protein MAVS.J Virol. 2016 Jul 27;90(16):7219-7230. doi: 10.1128/JVI.00221-16. Print 2016 Aug 15. J Virol. 2016. PMID: 27252539 Free PMC article.
-
MAVS-mediated host cell defense is inhibited by Borna disease virus.Int J Biochem Cell Biol. 2013 Aug;45(8):1546-55. doi: 10.1016/j.biocel.2013.05.012. Epub 2013 May 20. Int J Biochem Cell Biol. 2013. PMID: 23702035
-
Dissociation of a MAVS/IPS-1/VISA/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage.J Virol. 2006 Jun;80(12):6072-83. doi: 10.1128/JVI.02495-05. J Virol. 2006. PMID: 16731946 Free PMC article.
-
MasterCARD: a priceless link to innate immunity.Trends Mol Med. 2006 Feb;12(2):53-6. doi: 10.1016/j.molmed.2005.12.003. Epub 2006 Jan 6. Trends Mol Med. 2006. PMID: 16406812 Review.
Cited by
-
Therapeutic efficacy of a novel self-assembled immunostimulatory siRNA combining apoptosis promotion with RIG-I activation in gliomas.J Transl Med. 2024 Apr 29;22(1):395. doi: 10.1186/s12967-024-05151-5. J Transl Med. 2024. PMID: 38685028 Free PMC article.
-
SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination.PLoS Pathog. 2023 Nov 13;19(11):e1011792. doi: 10.1371/journal.ppat.1011792. eCollection 2023 Nov. PLoS Pathog. 2023. PMID: 37956198 Free PMC article.
-
Mitochondrial antiviral signaling protein: a potential therapeutic target in renal disease.Front Immunol. 2023 Oct 12;14:1266461. doi: 10.3389/fimmu.2023.1266461. eCollection 2023. Front Immunol. 2023. PMID: 37901251 Free PMC article. Review.
-
Novel insights into double-stranded RNA-mediated immunopathology.Nat Rev Immunol. 2024 Apr;24(4):235-249. doi: 10.1038/s41577-023-00940-3. Epub 2023 Sep 26. Nat Rev Immunol. 2024. PMID: 37752355 Review.
-
Overexpression of the mitochondrial anti-viral signaling protein, MAVS, in cancers is associated with cell survival and inflammation.Mol Ther Nucleic Acids. 2023 Jul 17;33:713-732. doi: 10.1016/j.omtn.2023.07.008. eCollection 2023 Sep 12. Mol Ther Nucleic Acids. 2023. PMID: 37662967 Free PMC article.
References
-
- Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005;122:669–682. - PubMed
-
- Kawai T, Takahashi K, Sato S, Coban C, Kumar H, et al. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol. 2005;6:981–988. - PubMed
-
- Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, et al. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005;19:727–740. - PubMed
-
- Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005;437:1167–1172. - PubMed
-
- Sun Q, Sun L, Liu HH, Chen X, Seth RB, et al. The specific and essential role of MAVS in antiviral innate immune responses. Immunity. 2006;24:633–642. - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous