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针对小反刍兽疫病毒 M mRNA 的小干扰 RNA 可增加病毒介导的融合性,并抑制病毒在体外的复制。

Small interfering RNAs targeting peste des petits ruminants virus M mRNA increase virus-mediated fusogenicity and inhibit viral replication in vitro.

机构信息

OIE Reference Laboratory for Peste des Petits Ruminants, National Research Center for Exotic Animal Diseases, China Animal Health and Epidemiology Center, No. 369 Nanjing Road, Qingdao, Shandong 266032, China.

OIE Reference Laboratory for Peste des Petits Ruminants, National Research Center for Exotic Animal Diseases, China Animal Health and Epidemiology Center, No. 369 Nanjing Road, Qingdao, Shandong 266032, China.

出版信息

Antiviral Res. 2015 Nov;123:22-6. doi: 10.1016/j.antiviral.2015.08.011. Epub 2015 Aug 25.

Abstract

Peste des petits ruminants (PPR), caused by peste des petits ruminants virus (PPRV), is an acute or subacute, highly contagious and economically important disease of small ruminants. The PPRV is classified into the genus Morbillivirus in the family Paramyxoviridae. The PPRV matrix (M) protein possesses an intrinsic ability to bind to lipid membranes, and plays a crucial role in viral assembly and further budding. In this study, three different small interfering RNAs (siRNA) were designed on the basis of translated region for PPRV Nigeria 75/1M mRNA, and were subsequently synthesized for their transfection into Vero-SLAM cells, followed by infection with PPRVs. The results showed that two out of three siRNAs robustly induced cell-to-cell fusion as early as 36h post-infection with PPRVs, effectively suppressed expression of the M protein by interference for the M mRNA, and eventually inhibited viral replication in vitro. These findings led us to speculate that siRNA-mediated knockdown of the M protein would alter its interaction with viral glycoproteins, thus exacerbating intercellular fusion but hampering virus release.

摘要

小反刍兽疫(PPR)是由小反刍兽疫病毒(PPRV)引起的一种急性或亚急性、高度接触传染性和经济上重要的小反刍动物疾病。PPRV 被分类为副黏病毒科麻疹病毒属的病毒。PPRV 的基质(M)蛋白具有与脂膜结合的内在能力,在病毒组装和进一步出芽过程中发挥关键作用。在这项研究中,根据 PPRV 尼日利亚 75/1M mRNA 的翻译区设计了三种不同的小干扰 RNA(siRNA),并随后将其合成用于转染 Vero-SLAM 细胞,然后用 PPRV 感染。结果表明,三种 siRNA 中有两种在感染 PPRV 后 36 小时即可强烈诱导细胞间融合,有效地通过干扰 M mRNA 抑制 M 蛋白的表达,并最终抑制病毒在体外复制。这些发现使我们推测,siRNA 介导的 M 蛋白敲低会改变其与病毒糖蛋白的相互作用,从而加剧细胞间融合,但阻碍病毒释放。

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