RRC ID 43248
著者 Dharel N, Kato N, Muroyama R, Taniguchi H, Otsuka M, Wang Y, Jazag A, Shao RX, Chang JH, Adler MK, Kawabe T, Omata M.
タイトル Potential contribution of tumor suppressor p53 in the host defense against hepatitis C virus.
ジャーナル Hepatology
Abstract UNLABELLED:Infection by hepatitis C virus (HCV) usually results into chronic hepatitis that can ultimately lead to cirrhosis and hepatocellular carcinoma. Type 1 interferons (IFN-alpha/beta) constitute the primary cellular defense against viral infection including HCV. IFN binding to their receptors activates associated Jak1 and Tyk2 kinases, which ultimately leads to phosphorylation and assembly of a signal transducer and activator of transcription protein (STAT)1-STAT2-interferon regulatory factor (IRF)9 trimetric complex called interferon-stimulated gene factor 3 that translocates into the nucleus and binds to the interferon- stimulated response elements (ISRE), leading to transcriptional induction of several antiviral genes, including double-stranded RNA-activated protein kinase (PKR), 2',5'- oligoadenylate synthetase (OAS), and myxovirus resistance protein A (MxA). Understanding the mechanisms of how the virus evades this cellular innate defense and establishes a chronic infection is the key for the development of better therapeutics against HCV infection. Here, we demonstrate that p53 could have a crucial role in the cellular innate defense against HCV. We observed significantly higher levels of HCV RNA replication and viral protein expression in the Huh7 cells when their p53 expressions were knocked down. Moreover, IFN treatment was less effective in inhibiting the HCV RNA replication in the p53-knocked-down (p53kd) Huh7 cells. In fact, the activation of the ISRE and the induction of ISGs were significantly attenuated in the p53kd Huh7 cells and p53 was found to directly interact with IRF9.
CONCLUSION:These observations underscore the potential contributions of the tumor suppressor p53 in cellular antiviral immunity against HCV with possible therapeutic implications.
巻・号 47(4)
ページ 1136-49
公開日 2008-4-1
DOI 10.1002/hep.22176
PMID 18220274
MeSH Cell Cycle / immunology Cell Line, Tumor Cell Nucleus / metabolism Cell Proliferation Gene Expression Hepacivirus / immunology* Hepacivirus / physiology Hepatitis C / drug therapy Hepatitis C / immunology* Host-Pathogen Interactions / immunology* Humans Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism Interferons / therapeutic use Replicon / immunology Tumor Suppressor Protein p53 / immunology* Tumor Suppressor Protein p53 / metabolism Viral Proteins / metabolism Virus Replication / physiology
IF 14.679
引用数 49
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞 HuH-7(RCB1366) HuH-6(RCb1367)