A mouse polyomavirus-encoded microRNA targets the cellular apoptosis pathway through Smad2 inhibition.

A mouse polyomavirus-encoded microRNA targets the cellular apoptosis pathway through Smad2 inhibition.
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DOI:
10.1016/j.virol.2014.07.052
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发表时间:
2014-11
期刊:
影响因子:
3.7
通讯作者:
Benjamin, Thomas L.
Benjamin, Thomas L.
中科院分区:
医学3区
文献类型:
--
作者:
Sung, Chang Kyoo;Yim, Hyungshin;Andrews, Erik;Benjamin, Thomas L.

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一些病毒和大多数真核细胞具有调节许多基因表达的microrna。虽然已经鉴定了许多病毒mirna,但只有少数被纳入体内功能研究。本研究表明,py编码的miRNA下调促凋亡因子Smad2的表达,从而抑制凋亡途径。为了在体内研究Py miRNA,在LID病毒株的背景下,创建了一个miRNA缺陷突变病毒,该病毒在新生小鼠中建立了快速致死感染。对肾脏组织的凋亡分析表明,促凋亡途径在感染宿主中也是靶向的。Py miRNA通过靶向Smad2抑制细胞凋亡,有望与先前归因于多瘤肿瘤抗原的抗凋亡作用协同,支持病毒在自然宿主中的复制。
Some viruses and most eukaryotic cells have microRNAs that regulate the expression of many genes. Although many viral miRNAs have been identified, only a few have been included in in vivo functional studies. Here we show that a Py-encoded miRNA downregulates the expression of the pro-apoptotic factor Smad2, resulting in the suppression of the apoptosis pathway. To study the Py miRNA in an in vivo context, a miRNA-deficient mutant virus was created on the background of the LID virus strain which establishes a rapid and lethal infection in newborn mice. Apoptosis analysis on kidney tissues indicates that the pro-apoptotic pathway is targeted in the infected host as well. Suppression of apoptosis through targeting of Smad2 by the Py miRNA is expected to synergize with anti-apoptotic effects previously attributed to the polyoma tumor antigens in support of virus replication in the natural host.
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