Cellular microRNAs 498 and 320d regulate herpes simplex virus 1 induction of Kaposi's sarcoma-associated herpesvirus lytic replication by targeting RTA.
Cellular microRNAs 498 and 320d regulate herpes simplex virus 1 induction of Kaposi's sarcoma-associated herpesvirus lytic replication by targeting RTA.
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DOI：
10.1371/journal.pone.0055832
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lu C
中科院分区：
文献类型：
--
作者：
Yan Q;Li W;Tang Q;Yao S;Lv Z;Feng N;Ma X;Bai Z;Zeng Y;Qin D;Lu C
卡波西肉瘤相关疱疹病毒 (KSHV) 感染对于 KS 的发展是必要的，但在没有其他辅助因子的情况下还不够。我们之前报道过，单纯疱疹病毒（HSV）-1是一个重要的辅助因子，通过诱导KSHV复制和转录激活子（RTA）（裂解开关蛋白）的表达，将KSHV从潜伏期重新激活。在这里，我们进一步研究了 HSV-1 诱导的 KSHV 复制过程中可能参与 RTA 调节的细胞 microRNA (miRNA)。通过 miRNA 微阵列分析鉴定了模拟和 HSV-1 感染的体腔淋巴瘤 (BCBL-1) 细胞之间 miRNA 表达的差异谱。生物信息学和荧光素酶报告基因分析表明，两个 HSV-1 下调的细胞 miRNA，miR-498 和 miR-320d，直接靶向 KSHV RTA 的 3' 非翻译区 (UTR)。结果，这两种 miRNA 的过表达显着抑制了 HSV-1 诱导的 KSHV 复制，而用特异性抑制剂抑制这些 miRNA 则增强了 HSV-1 介导的 KSHV 复制。此外，在没有HSV-1感染的情况下，单独的miR-498或miR-320d可以调节BCBL-1细胞中KSHV的复制。最后，生物信息学基因本体（GO）分析表明，HSV-1调节的miRNA靶点富含蛋白质，其作用涉及蛋白质结合、酶活性、生物调节，并且包括转化生长因子（TGF）-β在内的多种潜在信号通路可能参与HSV-1诱导的KSHV复制。总的来说，这些新发现表明，宿主编码的 miR-498 和 miR-320d 通过靶向 RTA 来调节 HSV-1 诱导 KSHV 裂解性复制，这为控制 KSHV 裂解性复制的分子机制提供了进一步的见解。
Kaposi’s sarcoma-associated herpesvirus (KSHV) infection was necessary but not sufficient for KS development without other cofactors. We have previously reported that herpes simplex virus (HSV)-1 was an important cofactor that reactivated KSHV from latency by inducing the expression of KSHV replication and transcription activator (RTA), the lytic switch protein. Here, we further investigated the possible cellular microRNAs (miRNAs) involved in regulation of RTA during HSV-1-induced KSHV replication. The differential profiles of miRNAs expression between Mock- and HSV-1-infected body cavity-based lymphoma (BCBL-1) cells were identified by miRNA microarray analysis. Bioinformatics and luciferase reporter analyses showed that two of the HSV-1-downregulated cellular miRNAs, miR-498 and miR-320d, directly targeted the 3′ untranslated region (UTR) of KSHV RTA. As a result, overexpression of these two miRNAs significantly inhibited HSV-1-induced KSHV replication, whereas repression of these miRNAs with specific suppressors enhanced HSV-1-mediated KSHV replication. In addition, miR-498 or miR-320d alone, without HSV-1 infection, regulated KSHV replication in BCBL-1 cells. Finally, bioinformatics Gene Ontology (GO) analysis indicated that targets of HSV-1-regulated miRNAs were enriched for proteins, whose roles were involved in protein binding, enzyme activity, biological regulation, and several potential signaling pathways including transforming growth factor (TGF)-β were likely to participate in HSV-1-induced KSHV replication. Collectively, these novel findings demonstrated that host-encoded miR-498 and miR-320d regulated HSV-1 induction of KSHV lytic replication by targeting RTA, which provided further insights into the molecular mechanisms controlling KSHV lytic replication.
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影响因子：
3.2
作者：
Duan, Huihan;Jiang, Yiguo;Wu, Yan
通讯作者：
Wu, Yan
影响因子：
10.5
作者：
Hansen, Amy;Henderson, Stephen;Boshoff, Chris
通讯作者：
Boshoff, Chris
影响因子：
56.9
作者：
Jopling, CL;Yi, MK;Sarnow, P
通讯作者：
Sarnow, P
microRNA表达模式在人肝内胆管癌中的作用。
影响因子：
25.7
作者：
Chen, Lei;Yan, He-Xin;Wang, Hong-Yang
通讯作者：
Wang, Hong-Yang
DOI：
10.1006/clin.1994.1167
发表时间：
1994-10-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
LAMONTAGNE, L;JOLICOEUR, P
通讯作者：
JOLICOEUR, P