Regulation of NF-kappaB inhibitor IkappaBalpha and viral replication by a KSHV microRNA.
Regulation of NF-kappaB inhibitor IkappaBalpha and viral replication by a KSHV microRNA.
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DOI：
10.1038/ncb2019
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发表时间：
2010-02
影响因子：
21.3
通讯作者：
Gao, Shou-Jiang
中科院分区：
文献类型：
--
作者：
Lei, Xiufen;Bai, Zhiqiang;Ye, Fengchun;Xie, Jianping;Kim, Chan-Gil;Huang, Yufei;Gao, Shou-Jiang
卡波西肉瘤相关疱疹病毒（KSHV）与几种获得性免疫缺陷综合征相关的恶性肿瘤有因果关系，包括卡波西肉瘤（KS）、原发性渗出性淋巴瘤（PEL）和多中心Castleman病的一个子集。控制病毒裂解复制对于KSHV潜伏、逃避宿主免疫系统和诱导肿瘤是必不可少的。在这里，我们发现从KSHV基因组中删除一组14个microRNA（miR）显著增强了病毒裂解复制，这是NF-κB活性降低的结果。miR簇通过减少NF-κB复合物抑制剂IκBα蛋白的表达来调节NF-κB通路。计算和miR种子突变分析鉴定了直接介导IκBα？通过靶向其转录物的3 'UTR在蛋白水平上表达。miR-K1的表达足以拯救NF-κB活性并抑制病毒裂解复制，而在KSHV感染的PEL细胞中抑制miR-K1具有相反的作用。因此，KSHV编码一个miR，通过激活NF-κB途径控制病毒复制。这些结果说明了KSHV miR通过操纵宿主存活途径在调节病毒潜伏期和裂解性复制中的重要作用。
Kaposi’s sarcoma-associated herpesvirus (KSHV) is causally linked to several acquired immune deficiency syndrome related malignancies including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentric Castleman’s disease. Control of viral lytic replication is essential for KSHV latency, evasion of host immune system, and induction of tumors. Here, we show that deletion of a cluster of 14 microRNAs (miRs) from KSHV genome significantly enhances viral lytic replication as a result of reduced NF-κB activity. The miR cluster regulates NF-κB pathway by reducing the expression of IκBα protein, an inhibitor of the NF-κB complexes. Computational and miR seed mutagenesis analyses identify KSHV miR-K1 that directly mediates IκBα ?protein level by targeting the 3’UTR of its transcript. Expression of miR-K1 is sufficient to rescue the NF-κB activity and inhibit viral lytic replication while inhibition of miR-K1 in KSHV-infected PEL cells has the opposite effects. Thus, KSHV encodes a miR to control viral replication by activating NF-κB pathway. These results illustrate an important role for KSHV miRs in regulating viral latency and lytic replication by manipulating a host survival pathway.
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影响因子：
5.4
作者：
Skalsky, Rebecca L.;Samols, Mark A.;Renne, Rolf
通讯作者：
Renne, Rolf
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
4.5
作者：
Grundhoff, A;Sullivan, CS;Ganem, D
通讯作者：
Ganem, D
DOI：
10.1073/pnas.0711910105
发表时间：
2008-04-08
影响因子：
11.1
作者：
Murphy, Eain;Vanicek, Jiri;Levine, Arnold J.
通讯作者：
Levine, Arnold J.
影响因子：
5.4
作者：
Gottwein, Eva;Cai, Xuezhong;Cullen, Bryan R.
通讯作者：
Cullen, Bryan R.