| pubmed-article:16731946 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C0220847 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C1330957 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C0230839 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C1521991 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C0086168 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C0597304 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C1864770 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C0439855 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C0596311 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C1554978 | lld:lifeskim |
| pubmed-article:16731946 | lifeskim:mentions | umls-concept:C1549055 | lld:lifeskim |
| pubmed-article:16731946 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:16731946 | pubmed:dateCreated | 2006-5-29 | lld:pubmed |
| pubmed-article:16731946 | pubmed:abstractText | Intracellular RNA virus infection is detected by the cytoplasmic RNA helicase RIG-I that plays an essential role in signaling to the host antiviral response. Recently, the adapter molecule that links RIG-I sensing of incoming viral RNA to downstream signaling and gene activation events was characterized by four different groups; MAVS/IPS-1-1/VISA/Cardif contains an amino-terminal CARD domain and a carboxyl-terminal mitochondrial transmembrane sequence that localizes to the mitochondrial membrane. Furthermore, the hepatitis C virus NS3-4A protease complex specifically targets MAVS/IPS-1/VISA/Cardif for cleavage as part of its immune evasion strategy. With a novel search program written in python, we also identified an uncharacterized protein, KIAA1271 (K1271), containing a single CARD-like domain at the N terminus and a Leu-Val-rich C terminus that is identical to that of MAVS/IPS-1/VISA/Cardif. Using a combination of biochemical analysis, subcellular fractionation, and confocal microscopy, we now demonstrate that NS3-4A cleavage of MAVS/IPS-1/VISA/Cardif/K1271 results in its dissociation from the mitochondrial membrane and disrupts signaling to the antiviral immune response. Furthermore, virus-induced IKKepsilon kinase, but not TBK1, colocalized strongly with MAVS at the mitochondrial membrane, and the localization of both molecules was disrupted by NS3-4A expression. Mutation of the critical cysteine 508 to alanine was sufficient to maintain mitochondrial localization of MAVS/IPS-1/VISA/Cardif and IKKepsilon in the presence of NS3-4A. These observations provide an outline of the mechanism by which hepatitis C virus evades the interferon antiviral response. | lld:pubmed |
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| pubmed-article:16731946 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16731946 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16731946 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16731946 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16731946 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:16731946 | pubmed:issn | 0022-538X | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:JulkunenIlkka... | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:LinRongtuanR | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:HiscottJohnJ | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:MeursElianeE | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:SunQiangQ | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:YangLongL | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:VitourDamienD | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:WilkinsonPete... | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:LacosteJudith... | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:NakhaeiPeyman... | lld:pubmed |
| pubmed-article:16731946 | pubmed:author | pubmed-author:PazSuzanneS | lld:pubmed |
| pubmed-article:16731946 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16731946 | pubmed:volume | 80 | lld:pubmed |
| pubmed-article:16731946 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16731946 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16731946 | pubmed:pagination | 6072-83 | lld:pubmed |
| pubmed-article:16731946 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:16731946 | pubmed:year | 2006 | lld:pubmed |
