Quinolinate Phosphoribosyltransferase is an Antiviral Host Factor Against Hepatitis C Virus Infection

文献类型： 外文期刊

第一作者： Wang, Zhilong

作者： Wang, Zhilong;Hu, Haiming;Xu, Qiuping;Zhang, Weihong;Deng, Sisi;Lv, Pingyun;Yang, Yan;Chen, Xinwen;Tang, Hong;Wang, Zhilong;Hu, Haiming;Xu, Qiuping;Zhang, Weihong;Deng, Sisi;Lv, Pingyun;Yang, Yan;Chen, Xinwen;Tang, Hong;Gao, Yanhang;Gong, Sitang;Xu, Yi;Gong, Sitang;Wang, Zhilong;Zhang, Chao;Chen, Hairong;Tang, Hong;Xu, Qiuping;Tang, Hong;Guo, Dongwei;Weng, Changjiang;Gao, Yanhang;Ding, Yanhua;Li, Qingquan;Niu, Junqi;Wang, Zhilong

作者机构：

期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.379； 五年影响因子：5.133 ）

ISSN： 2045-2322

年卷期： 2017 年 7 卷

页码：

收录情况： SCI

摘要： HCV infection can decrease NAD(+)/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes, quinolinate phosphoribosyl transferase (QPRT) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates QPRT hence the lipogenesis is unknown. In this work, we found QPRT was reduced significantly in livers of patients or humanized C/O-Tg mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7.5.1 cells. Furthermore, QPRT enzymatic activity involved in suppression of HCV replication in cells. Activation of QPRT with clofibrate (CLO) or addition of QPRT catabolite NAD both inhibited HCV replication in cells, probably through NAD(+)-dependent Sirt1 inhibition of cellular lipogenesis. More importantly, administration of CLO, a hypolipidemic drug used in clinics, could significantly reduce the viral load in HCV infected C/O-Tg mice. Take together, these results suggested that HCV infection triggered proteasomal degradation of QPRT and consequently reduced de novo NAD synthesis and lipogenesis, in favor of HCV replication. Hepatic QPRT thus likely served as a cellular factor that dampened productive HCV replication.

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