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Regulation of nf-kappa b inhibitor i kappa b alpha and viral replication by a kshv microrna
Lei, Xiufen1,2,3; Bai, Zhiqiang1,2,3,4,5; Ye, Fengchun1,2,3; Xie, Jianping1,2,3; Kim, Chan-Gil1,6; Huang, Yufei1,7; Gao, Shou-Jiang1,2,3,4,5
刊名Nature cell biology
2010-02-01
卷号12期号:2页码:193-u232
ISSN号1465-7392
DOI10.1038/ncb2019
通讯作者Gao, shou-jiang(gaos@uthscsa.edu)
英文摘要Kaposi's sarcoma-associated herpesvirus (kshv) is causally linked to several acquired immune deficiency syndrome-related malignancies, including kaposi's sarcoma, primary effusion lymphoma (pel) and a subset of multicentric castleman's disease(1). control of viral lytic replication is essential for kshv latency, evasion of the host immune system and induction of tumours(1). here, we show that deletion of a 14 microrna (mirna) cluster from the kshv genome significantly enhances viral lytic replication as a result of reduced nf-kappa b activity. the mirna cluster regulates the nf-kappa b pathway by reducing expression of i kappa b alpha protein, an inhibitor of nf-kappa b complexes. computational and mirna seed mutagenesis analyses were used to identify kshv mir-k1, which directly regulates the i kappa b alpha protein level by targeting the 3'utr of its transcript. expression of mir-k1 is sufficient to rescue nf-kappa b activity and inhibit viral lytic replication, whereas inhibition of mir-k1 in kshv-infected pel cells has the opposite effect. thus, kshv encodes an mirna to control viral replication by activating the nf-kappa b pathway. these results demonstrate an important role for kshv mirnas in regulating viral latency and lytic replication by manipulating the host survival pathway.
WOS关键词SARCOMA-ASSOCIATED HERPESVIRUS ; EPSTEIN-BARR-VIRUS ; KAPOSIS-SARCOMA ; TRANSCRIPTIONAL PROGRAM ; GENE-EXPRESSION ; LATENT ; IDENTIFICATION ; INFECTION ; PATHWAY ; TARGETS
WOS研究方向Cell Biology
WOS类目Cell Biology
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000274139400014
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2375799
专题武汉病毒研究所
通讯作者Gao, Shou-Jiang
作者单位1.Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, Tumor Virol Program, San Antonio, TX 78229 USA
2.Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat Microbiol & Immunol Med & Mol Med, San Antonio, TX 78229 USA
3.Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA
4.Chinese Acad Sci, Wuhan Inst Virol, Tumor Virol Grp, Wuhan 430071, Hubei, Peoples R China
5.Chinese Acad Sci, Grad Univ, Beijing 100039, Peoples R China
6.Konkuk Univ, Dept Biotechnol, Chungju 380701, South Korea
7.Univ Texas San Antonio, Dept Elect & Comp Engn, San Antonio, TX 78249 USA
推荐引用方式
GB/T 7714
Lei, Xiufen,Bai, Zhiqiang,Ye, Fengchun,et al. Regulation of nf-kappa b inhibitor i kappa b alpha and viral replication by a kshv microrna[J]. Nature cell biology,2010,12(2):193-u232.
APA Lei, Xiufen.,Bai, Zhiqiang.,Ye, Fengchun.,Xie, Jianping.,Kim, Chan-Gil.,...&Gao, Shou-Jiang.(2010).Regulation of nf-kappa b inhibitor i kappa b alpha and viral replication by a kshv microrna.Nature cell biology,12(2),193-u232.
MLA Lei, Xiufen,et al."Regulation of nf-kappa b inhibitor i kappa b alpha and viral replication by a kshv microrna".Nature cell biology 12.2(2010):193-u232.
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