CD2-Associated Protein Contributes to Hepatitis C, Virus Propagation and Steatosis by Disrupting Insulin Signaling.
CD2-Associated Protein Contributes to Hepatitis C, Virus Propagation and Steatosis by Disrupting Insulin Signaling.
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CD2 相关蛋白通过破坏胰岛素信号传导导致丙型肝炎、病毒传播和脂肪变性
DOI：
10.1002/hep.30073
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Zhang H;Zhang C;Tang H;Gao S;Sun F;Yang Y;Zhou W;Hu Y;Ke C;Wu Y;Ding Z;Guo L;Pei R;Chen X;Sy MS;Zhang B;Li C
慢性丙型肝炎病毒（HCV）感染可导致脂肪变性，这是一种显示中性脂质囊泡（脂滴（LD）的组分）异常积聚的病症，其对于HCV组装至关重要。然而，HCV感染和脂肪变性之间的相互作用仍不清楚。在这里，我们发现HCV感染的细胞具有更高水平的CD 2相关蛋白（CD 2AP），其在HCV发病机制中起着两种不同但紧密相关的作用：升高的CD 2AP与非结构蛋白5A（NS 5A）结合，并参与NS 5A向LD的转运，以促进病毒组装;上调的CD 2AP也与Casitas B谱系淋巴瘤相互作用（B）（Cbl/Cbl-B）E3连接酶降解胰岛素受体底物1（IRS 1），反过来，通过IRS 1/蛋白激酶B（Akt）/腺苷一磷酸活化蛋白激酶（AMPK）/激素敏感脂肪酶（HSL）信号传导轴破坏胰岛素信号传导并增加LD蓄积，以适应病毒组装。在HCV感染的小鼠模型中，CD 2AP表达在慢性感染阶段上调，这种上调与肝脏脂肪变性密切相关。重要的是，与非HCV感染的对照相比，在显示脂肪变性的HCV感染的人肝活检中也检测到CD 2AP上调。结论：CD 2AP是一种受HCV感染上调的蛋白质，进而通过破坏胰岛素信号传导刺激HCV传播和脂肪变性;靶向CD 2AP可能为缓解HCV感染及其相关肝脏病理提供机会。（肝病学2018;XX：XXX-XXX。）
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. (Hepatology 2018;XX:XXX‐XXX.)
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影响因子：
82.9
作者：
通讯作者：
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影响因子：
6.7
作者：
Coller KE;Berger KL;Heaton NS;Cooper JD;Yoon R;Randall G
通讯作者：
Randall G
DOI：
10.1007/s00018-012-1213-0
发表时间：
2013-04
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
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作者：
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通讯作者：
Roingeard P
DOI：
10.1083/jcb.201112098
发表时间：
2012-03-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Roux KJ;Kim DI;Raida M;Burke B
通讯作者：
Burke B
影响因子：
3.7
作者：
Shi, ST;Polyak, SJ;Lai, MMC
通讯作者：
Lai, MMC