Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses.

Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses.
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DOI:
10.1186/1742-4690-9-53
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发表时间:
2012-06-22
期刊:
影响因子:
3.3
通讯作者:
Malim MH
Malim MH
中科院分区:
医学2区
文献类型:
--
作者:
Arjan-Odedra S;Swanson CM;Sherer NM;Wolinsky SM;Malim MH

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识别调节外源病毒复制的细胞因子和内源移动元件有助于从根本上理解宿主与病原体之间的关系。MOV10是一种超家族1的RNA解旋酶,控制多种RNA病毒的复制,其同源基因是抑制内源移动元件所必需的。在这里,我们使用异位表达和基因敲除方法来分析人MOV10在一组外源性逆转录病毒和内源性逆转录病毒复制中的作用。MOV10的过表达显著减少了感染性逆转录病毒颗粒的产生,以及LTR和非LTR内源性逆转录元件的繁殖。最重要的是,RNAi介导的内源性MOV10沉默促进了内源性和非内源性逆转录元件的复制,但不能增加感染性逆转录病毒颗粒的产生,这表明自然水平的MOV10抑制了逆转录转座,但对外源性逆转录病毒的感染没有影响。此外,功能研究表明,MOV10不是miRNA或siRNA介导的mRNA沉默所必需的。我们已经确定了人MOV10在控制逆转录元件复制方面的新的特异性,并假设MOV10可能是选择性地调节体细胞内源性逆转录元件复制的细胞途径或过程的一个组成部分。
The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells.
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