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    CD2‐Associated Protein Contributes to Hepatitis C, Virus Propagation and Steatosis by Disrupting Insulin Signaling, Hepatology, Nov 2018
    2018-11-01 | 【     】【打印】【关闭

    Hepatology, November 2018,DOI: https://doi.org/10.1002/hep.30073

    CD2‐Associated Protein Contributes to Hepatitis C, Virus Propagation and Steatosis by Disrupting Insulin Signaling

    Huixia Zhang  Chao Zhang  Hong Tang  Shanshan Gao  Fang Sun  Yuan Yang  Weiping Zhou  Yu Hu Changshu Ke  Yu Wu  Zeyang Ding  Lin Guo  Rongjuan Pei  Xinwen Chen  Man‐Sun Sy Bixiang Zhang  Chaoyang Li

    Abstract

    Chronic hepatitis C virus (HCV) infection can result in steatosis, a condition displaying aberrant accumulation of neutral lipid vesicles, the component of lipid droplets (LDs), which are essential for HCV assembly. However, the interplay between HCV infection and steatosis remains unclear. Here, we show that HCV‐infected cells have higher levels of CD2‐associated protein (CD2AP), which plays two distinct, yet tightly linked, roles in HCV pathogenesis: Elevated CD2AP binds to nonstructural protein 5A (NS5A) and participates in the transport of NS5A to LDs to facilitate viral assembly; Up‐regulated CD2AP also interacts with casitas B‐lineage lymphoma (b) (Cbl/Cbl‐b) E3 ligases to degrade insulin receptor substrate 1 (IRS1), which, in turn, disrupts insulin signaling and increases LD accumulation through the IRS1/protein kinase B (Akt)/adenosine monophosphate‐activated protein kinase (AMPK)/hormone‐sensitive lipase (HSL) signaling axis to accommodate viral assembly. In the HCV‐infected mouse model, CD2AP expression is up‐regulated during the chronic infection stage and this up‐regulation correlates well with liver steatosis. Importantly, CD2AP up‐regulation was also detected in HCV‐infected human liver biopsies showing steatosis compared to non‐HCV‐infected controls. Conclusion: CD2AP is indicated as a protein up‐regulated by HCV infection, which, in turn, stimulates HCV propagation and steatosis by disrupting insulin signaling; targeting CD2AP may offer an opportunity for alleviating HCV infection and its associated liver pathology .

    文章链接:https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.30073

     

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  • 围甲北京德比中信主将负民生银行 时越逆转胜陈耀烨 2019-03-18
  • [微笑]商品价格受供需关系影响围绕价值上下波动!房价为什么高?炒作改变了供需关系! 2019-03-18
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  • 我的跟帖出不来,讨论不了,奈何?还以为版主护着我么?! 2019-02-13