Cellular miR-130b inhibits replication of porcine reproductive and respiratory syndrome virus in vitro and in vivo.
Cellular miR-130b inhibits replication of porcine reproductive and respiratory syndrome virus in vitro and in vivo.
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DOI：
10.1038/srep17010
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发表时间：
2015-11-19
影响因子：
4.6
通讯作者：
Tong G
中科院分区：
文献类型：
--
作者：
Li L;Gao F;Jiang Y;Yu L;Zhou Y;Zheng H;Tong W;Yang S;Xia T;Qu Z;Tong G
MicroRNAs(MiRNAs)可以通过与病毒RNA转录本上部分互补的序列结合来影响病毒感染，通常导致抑制病毒复制。在本研究中，我们在猪繁殖与呼吸综合征病毒(PRRSV)基因组的5‘非翻译区(BPS 155-162)确定了miR-130的一个潜在结合位点。我们发现，多个miR-130家族模拟物的传递，特别是miR-130b，在体外可以抑制PRRSV的复制。MIR-130对多种2型PRRSV株的复制有抑制作用，但对典型的1型毒株vSHE无明显抑制作用。在未感染或PRRSV感染的猪肺泡巨噬细胞中，miR-130过表达均不能诱导干扰素-α或肿瘤坏死因子-α的表达。荧光素酶分析结果表明，miR-130直接靶向PRRSV 5‘端非编码区。经鼻接种miR-130b的仔猪在体内表现出抗病毒活性，并部分保护仔猪免受HP-PRRSV毒株vJX143的致死攻击。总之，这些结果证明了miR-130家族在调节PRRSV复制中的重要性，并为在抗PRRSV治疗中使用细胞miRNAs提供了科学依据。
MicroRNAs (miRNAs) can impact viral infections by binding to sequences with partial complementarity on viral RNA transcripts, usually resulting in the repression of virus replication. In the present study, we identified a potential binding site for miR-130 in the 5′ untranslated region (bps 155-162) of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. We found that the delivery of multiple miR-130 family mimics, especially miR-130b, resulted in inhibition of PRRSV replication in vitro. miR-130 was effective in inhibiting the replication of multiple type 2 PRRSV strains, but not against vSHE, a classical type 1 strain. miR-130 over-expression did not induce IFN-α or TNF-α expression in either uninfected or PRRSV-infected porcine alveolar macrophages. Results from luciferase reporter assays indicated that miR-130 directly targeted the PRRSV 5′ UTR. Intranasal inoculation of piglets with miR-130b exhibited antiviral activity in vivo and partially protected piglets from an otherwise lethal challenge with HP-PRRSV strain vJX143. Overall, these results demonstrate the importance of the miR-130 family in modulating PRRSV replication and also provide a scientific basis for using cellular miRNAs in anti-PRRSV therapies.