The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity
Open accessAbstract
Hepatitis C virus (HCV) is a global epidemic manifested mainly by chronic infection. One strategy that HCV employs to establish chronic infection is to use the viral Ser protease NS3/4A to cleave some unknown cellular targets involved in innate immunity. Here we show that the target of NS3/4A is the mitochondrial antiviral signaling protein, MAVS, that activates NF-κB and IFN regulatory factor 3 to induce type-I interferons. NS3/4A cleaves MAVS at Cys-508, resulting in the dislocation of the N-terminal fragment of MAVS from the mitochondria. Remarkably, a point mutation of MAVS at Cys-508 renders MAVS resistant to cleavage by NS3/4A, thus maintaining the ability of MAVS to induce interferons in HCV replicon cells. NS3/4A binds to and colocalizes with MAVS in the mitochondrial membrane, and it can cleave MAVS directly in vitro . These results provide an example of host–pathogen interaction in which the virus evades innate immunity by dislodging a pivotal antiviral protein from the mitochondria and suggest that blocking the cleavage of MAVS by NS3/4A may be applied to the prevention and treatment of HCV.
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Self-citationIPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
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Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401
Decoding the Patterns of Self and Nonself by the Innate Immune System
Medzhitov, R., & Janeway, C. A. (2002) · Science · doi:10.1126/science.1068883 · Cited by 2,154
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Self-citation
Cited by
The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling
O'Neill, L. A. J., & Bowie, A. G. (2007) · Nature Reviews Immunology · doi:10.1038/nri2079 · Cited by 2,667
Mitochondria in innate immune responses
West, A. P., Shadel, G. S., & Ghosh, S. (2011) · Nature Reviews Immunology · doi:10.1038/nri2975 · Cited by 1,376
Intracellular pattern recognition receptors in the host response
Meylan, E., Tschopp, J., & Karin, M. (2006) · Nature · doi:10.1038/nature04946 · Cited by 1,206
The immunology of hepatocellular carcinoma
Ringelhan, M., Pfister, D., O’Connor, T., Pikarsky, E., & Heikenwalder, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0044-z · Cited by 1,076
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Creagh, E. M., & O’Neill, L. A. J. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.06.003 · Cited by 762
Metadata
- Authors
- Li, X.-D., Sun, L., Seth, R. B., Pineda, G., & Chen, Z. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-11-21
- Volume
- 102
- Issue
- 49
- Pages
- 17717-17722
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2013092102
- Cited by
- 840
- References
- 6
- FWCI
- 22.51
- Type
- journal article
- Language
- en
- Open access
- green
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- Li, X.-D., Sun, L., Seth, R. B., Pineda, G., & Chen, Z. J. (2005). Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0508531102
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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