Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively.
Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively.
复制标题
野猪 miR-204 和 miR-4331 分别通过靶向病毒 HA 和 NS 负调控猪 H1N1/2009 甲型流感病毒复制
DOI：
10.3390/ijms18040749
复制
发表时间：
2017-04-03
影响因子：
5.6
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Zhang S;Wang R;Su H;Wang B;Sizhu S;Lei Z;Jin M;Chen H;Cao J;Zhou H
H1N1/2009甲型流感病毒（SIV-H1N1/2009）在猪群中的流行具有产生新型抗病毒的潜力，对人类健康构成极大威胁。细胞微小RNA（microRNAs，miRNAs）是一种很有前途的小分子，可以直接靶向病毒基因组RNA，调控甲型流感病毒的复制。在本研究中，我们通过RegRNA 2.0预测了靶向SIV-H1N1/2009基因组RNA的潜在Sus scrofa（ssc-，猪）miRNAs，并通过双荧光素酶报告基因测定鉴定了ssc-miR-204和ssc-miR-4331分别靶向病毒HA和NS。分别过表达ssc-miR-204和ssc-miR-4331的新生猪气管（NPTr）细胞感染SIV-H1N1/2009后，病毒HA和NS的mRNA水平显著降低，而分别用抑制剂降低内源性ssc-miR-204和ssc-miR-4331后，抑制效果可恢复。由于病毒HA和NS在甲型流感病毒生命周期中的重要性，ssc-miR-204和ssc-miR-4331对SIV-H1N1/2009复制表现出抑制作用。由于H5 N1和H9 N2亚型流感病毒HA和NS的靶位点不保守，因此，SIV-H1N1/2009具有序列特异性抗病毒作用。此外，SIV-H1N1/2009感染可下调ssc-miR-204和ssc-miR-4331的表达，这可能有助于病毒在宿主体内的复制。综上所述，本研究为控制猪群中SIV-H1N1/2009的流行提供了重要线索。
The prevalence of swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) in pigs has the potential to generate novel reassortant viruses, posing a great threat to human health. Cellular microRNAs (miRNAs) have been proven as promising small molecules for regulating influenza A virus replication by directly targeting viral genomic RNA. In this study, we predicted potential Sus scrofa (ssc-, swine) miRNAs targeting the genomic RNA of SIV-H1N1/2009 by RegRNA 2.0, and identified ssc-miR-204 and ssc-miR-4331 to target viral HA and NS respectively through dual-luciferase reporter assays. The messenger RNA (mRNA) levels of viral HA and NS were significantly suppressed when newborn pig trachea (NPTr) cells respectively overexpressed ssc-miR-204 and ssc-miR-4331 and were infected with SIV-H1N1/2009, whereas the suppression effect could be restored when respectively decreasing endogenous ssc-miR-204 and ssc-miR-4331 with inhibitors. Because of the importance of viral HA and NS in the life cycle of influenza A virus, ssc-miR-204 and ssc-miR-4331 exhibited an inhibition effect on SIV-H1N1/2009 replication. The antiviral effect was sequence-specific of SIV-H1N1/2009, for the target sites in HA and NS of H5N1 or H9N2 influenza A virus were not conserved. Furthermore, SIV-H1N1/2009 infection reversely downregulated the expression of ssc-miR-204 and ssc-miR-4331, which might facilitate the virus replication in the host. In summary, this work will provide us some important clues for controlling the prevalence of SIV-H1N1/2009 in pig populations.
从猪中分离出的 2009 年大流行 (H1N1) 病毒对小鼠的致病性增强
影响因子：
4.4
作者：
Li Y;Zou W;Jia G;Ke J;Zhu J;Lin X;Zhou H;Jin M
通讯作者：
Jin M