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	Quinolinate phosphoribosyltransferase is an antiviral host factor against hepatitis c virus infection
	Wang, Zhilong1,2,5,9; Gao, Yanhang3,8; Zhang, Chao5; Hu, Haiming1,2; Guo, Dongwei7; Xu, Yi4; Xu, Qiuping1,2,6; Zhang, Weihong1,2; Deng, Sisi1,2; Lv, Pingyun1,2
刊名	Scientific reports
	2017-07-19
卷号	7页码:10
ISSN号	2045-2322
DOI	10.1038/s41598-017-06254-4
通讯作者	Tang, hong(htang@ips.ac.cn)
英文摘要	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.
WOS关键词	METABOLISM DISORDERS ; LIPID-METABOLISM ; RIG-I ; PROTEIN ; UBIQUITINATION ; REPLICATION ; SYSTEMS ; MICE ; POLY(ADP-RIBOSE) ; DEGRADATION
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000405895000028
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2373410
专题	武汉病毒研究所
通讯作者	Tang, Hong
作者单位	1.Chinese Acad Sci, Wuhan Inst Virol, Joint Lab Translat Precis Med, Wuhan 430071, Hubei, Peoples R China 2.Chinese Acad Sci, Guangzhou Women & Children` s Med Ctr, Wuhan Inst Virol, Wuhan 430071, Hubei, Peoples R China 3.Chinese Acad Sci, Wuhan Inst Virol, Joint Lab Translat Precis Med, Guangzhou 510623, Guangdong, Peoples R China 4.Guangzhou Women & Childrens Med Ctr, Guangzhou 510623, Guangdong, Peoples R China 5.Chinese Acad Sci, Inst Biophys, CAS Key Lab Infect & Immun, Beijing 100101, Peoples R China 6.Chinese Acad Sci, Inst Pasteur Shanghai, Shanghai 200031, Peoples R China 7.Chinese Acad Agr Sci, Harbin Vet Res Inst, Harbin 150001, Heilongjiang, Peoples R China 8.Jilin Univ, Dept Hepatol, Hosp 1, Changchun 130021, Jilin, Peoples R China 9.Univ Chinese Acad Sci, Beijing 10049, Peoples R China
推荐引用方式 GB/T 7714	Wang, Zhilong,Gao, Yanhang,Zhang, Chao,et al. Quinolinate phosphoribosyltransferase is an antiviral host factor against hepatitis c virus infection[J]. Scientific reports,2017,7:10.
APA	Wang, Zhilong.,Gao, Yanhang.,Zhang, Chao.,Hu, Haiming.,Guo, Dongwei.,...&Tang, Hong.(2017).Quinolinate phosphoribosyltransferase is an antiviral host factor against hepatitis c virus infection.Scientific reports,7,10.
MLA	Wang, Zhilong,et al."Quinolinate phosphoribosyltransferase is an antiviral host factor against hepatitis c virus infection".Scientific reports 7(2017):10.

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