Cyclosporine inhibits flavivirus replication through blocking the interaction between host cyclophilins and viral ns5 protein
文献类型：期刊论文
| 作者 | Qing, Min1,2; Yang, Feng3; Zhang, Bo2; Zou, Gang1,2; Robida, John M.3; Yuan, Zhiming1; Tang, Hengli3; Shi, Pei-Yong2,4 |
| 刊名 | Antimicrobial agents and chemotherapy
 |
| 出版日期 | 2009-08-01 |
| 卷号 | 53期号:8页码:3226-3235 |
| ISSN号 | 0066-4804 |
| DOI | 10.1128/aac.00189-09 |
| 通讯作者 | Shi, pei-yong(pei_yong.shi@novartis.com) |
| 英文摘要 | Although flaviviruses cause significant human diseases, no effective therapy is currently available. host factors essential for viral replication are potential targets for antiviral development. here we report that cyclophilins (cyps), a family of cellular peptidyl-prolyl isomerases (ppiases), play a role in flavivirus replication. huh-7.5 cells with knockdown of different isoforms of cyp were less efficient than parental cells in supporting flavivirus replication, including west nile virus (wnv), dengue virus, and yellow fever virus. the low viral replication in cyp a (cypa) knockdown cells could be rescued by trans supplying of a wild-type cypa but not by trans supplying of a mutant cypa (defective in the ppiase activity), indicating that the isomerase activity of cypa is critical for viral replication. immunoprecipitation and biochemical pulldown analyses showed that cypa interacts with wnv genomic rna and viral ns5 protein in the replication complex. furthermore, antiviral experiments demonstrated that cyclosporine (cs; an 11-amino-acid cyclic peptide known to block the ppiase activity of cypa) inhibits flavivirus replication in cell culture at nontoxic concentrations. time-of-addition and transient replicon results indicated that cs inhibits flavivirus at the step of viral rna synthesis. biochemical analysis showed that cs directly blocks the interaction between cypa and wnv ns5 protein. our results suggest that host cypa is a component of flavivirus replication complex and could be targeted for potential antiviral development. |
| WOS关键词 | WEST-NILE-VIRUS ; HUMAN-IMMUNODEFICIENCY-VIRUS ; HEPATITIS-C-VIRUS ; RNA-STIMULATED NTPASE ; DENGUE VIRUS ; IN-VITRO ; NUCLEOSIDE TRIPHOSPHATASE ; ALPHA-INTERFERON ; POLYMERASE NS5 ; SDZ NIM-811 |
| WOS研究方向 | Microbiology ; Pharmacology & Pharmacy |
| WOS类目 | Microbiology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000268098300007 |
| 出版者 | AMER SOC MICROBIOLOGY |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375621 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Shi, Pei-Yong |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China 2.New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA 3.Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA 4.SUNY Albany, Dept Biomed Sci, Albany, NY 12208 USA |
| 推荐引用方式 GB/T 7714 | Qing, Min,Yang, Feng,Zhang, Bo,et al. Cyclosporine inhibits flavivirus replication through blocking the interaction between host cyclophilins and viral ns5 protein[J]. Antimicrobial agents and chemotherapy,2009,53(8):3226-3235. |
| APA | Qing, Min.,Yang, Feng.,Zhang, Bo.,Zou, Gang.,Robida, John M..,...&Shi, Pei-Yong.(2009).Cyclosporine inhibits flavivirus replication through blocking the interaction between host cyclophilins and viral ns5 protein.Antimicrobial agents and chemotherapy,53(8),3226-3235. |
| MLA | Qing, Min,et al."Cyclosporine inhibits flavivirus replication through blocking the interaction between host cyclophilins and viral ns5 protein".Antimicrobial agents and chemotherapy 53.8(2009):3226-3235. |
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来源：武汉病毒研究所
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