BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus

doi:10.2174/1566524013666131118111719

科研成果详情

题名	BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus
作者	Amet T.1; Byrd D.1; Hu N.2; Sun Q.2; Li F.2; Zhao Y.2; Hu S.1,3; Grantham A.1; Yu Q.1,4
发表日期	2014-03
发表期刊	CURRENT MOLECULAR MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	BST-2 HCV host restriction factor Huh7.5.1 cell interferon lipid droplet
其他关键词	ADAPTIVE IMMUNE-RESPONSES ; SPONTANEOUS CLEARANCE ; GENETIC-VARIATION ; ALPHA-INTERFERON ; DOWN-MODULATION ; INDUCED PROTEIN ; CELL-SURFACE ; DRUG-USERS ; INFECTION ; IL28B
摘要	Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin, CD317, or HM1.24) has recently been identified as a host restriction factor against diverse families of enveloped viruses. However, the effects of BST-2 on the life cycle of hepatitis C virus (HCV), an enveloped RNA virus, remain unclear and controversial. Here we demonstrated that human hepatocytes including Huh7.5.1 cells, primary human hepatocytes (PHHs), and HepG2 cells constitutively expressed low to moderate levels of endogenous BST-2 on the cell surface, which could be robustly up-regulated by all three types of interferons (IFNs) such as IFN-alpha, IFN-gamma, and IFN-lambda IFN-alpha and IFN-gamma showed a synergistic effect in induction of BST-2 expression on human hepatocytes. Over-expression of BST-2 by BST-2-expressing vector transfection or up-regulation of BST-2 by IFN stimulation markedly suppressed HCV production, whereas shRNA-mediated depletion of endogenous BST-2 significantly enhanced HCV production in infected Huh7.5.1 cells. IFN-mediated anti-HCV activity was partially but significantly diminished by shRNA-mediated knockdown of BST-2 expression, indicating that BST-2 upregulation is directly involved in IFN-mediated inhibition of HCV production. We also found that both BST-2 and HCV core co-localized with intracellular lipid droplets (LDs), suggesting that BST-2-HCV interaction may take place around LDs as LDs constitute an important intracellular organelle for HCV assembly and replication. Taken together, our data suggest that BST-2 is a host restriction factor against HCV, and induction of BST-2 in hepatocytes could be one of the mechanisms by which current HCV standard therapy (IFN-alpha plus ribavirin) achieves a sustained virological response (SVR).
资助项目	Grand Challenges Explorations (GCE) Phase II grant through the Bill & Melinda Gates Foundation [OPP1035237]; NIH [1R21AI104268, T32 AI060519]; Showalter Research Trust Fund; NSFC [81101247, 81201259]; NSFZJ [Y2110608, Y2110580]; Research Facilities Improvement Program Grant from the National Center for Research Resources, NIH [C06 RR015481-01]
出版者	BENTHAM SCIENCE PUBL LTD
ISSN	1566-5240
EISSN	1875-5666
卷号	14 期号:3 页码:349-360
DOI	10.2174/1566524013666131118111719
页数	12
WOS类目	Medicine, Research & Experimental
WOS研究方向	Research & Experimental Medicine
WOS记录号	WOS:000333339100005
收录类别	SCIE ; SCOPUS
URL	查看原文
PubMed ID	24236455
SCOPUSEID	2-s2.0-84897433637
通讯作者地址	[Yu Q.]Department of Microbiology and Immunology and Center for AIDS Research, Indiana University School of Medicine,635 Barnhill Drive,United States
Scopus学科分类	Biochemistry;Molecular Medicine;Molecular Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/213292
专题	检验医学院（生命科学学院、生物学实验教学中心）_模式生物技术与应用重点实验室
通讯作者	Yu Q.
作者单位	1.Department of Microbiology and Immunology, Indiana University School ofMedicine,635 Barnhill Drive,United States; 2.Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of LifeSciences, Wenzhou Medical University,China; 3.College of Veterinary Medicine, Huazhong Agricultural University,No. 1 Shizishan Street,China; 4.Center for AIDS Research, Indiana University School ofMedicine,635 Barnhill Drive,United States
推荐引用方式 GB/T 7714	Amet T.,Byrd D.,Hu N.,et al. BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus[J]. CURRENT MOLECULAR MEDICINE,2014,14(3):349-360.
APA	Amet T.., Byrd D.., Hu N.., Sun Q.., Li F.., ... & Yu Q.. (2014). BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus. CURRENT MOLECULAR MEDICINE, 14(3), 349-360.
MLA	Amet T.,et al."BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus".CURRENT MOLECULAR MEDICINE 14.3(2014):349-360.