State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei Universitygrid.34418.3a, Wuhan, Hubei, China.
Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu, China.
J Virol. 2022 Aug 10;96(15):e0187421. doi: 10.1128/jvi.01874-21. Epub 2022 Jul 13.
RNA interference (RNAi) is a significant posttranscriptional gene silencing mechanism and can function as an antiviral immunity in eukaryotes. However, numerous viruses can evade this antiviral RNAi by encoding viral suppressors of RNA silencing (VSRs). Classical swine fever virus (CSFV), belonging to the genus , is the cause of classical swine fever (CSF), which has an enormous impact on animal health and the pig industry. Notably, little is known about how blocks RNAi in their host. In this paper, we uncovered that CSFV NS4A protein can antagonize RNAi efficiently in mammalian cells by binding to double-stranded RNA and small interfering RNA. In addition, the VSR activity of CSFV NS4A was conserved among . Furthermore, the replication of VSR-deficient CSFV was attenuated but could be restored by the deficiency of RNAi in mammalian cells. In conclusion, our studies uncovered that CSFV NS4A is a novel VSR that suppresses RNAi in mammalian cells and shed new light on knowledge about CSFV and other . It is well known that RNAi is an important posttranscriptional gene silencing mechanism that is also involved in the antiviral response in mammalian cells. While numerous viruses have evolved to block this antiviral immunity by encoding VSRs. Our data demonstrated that the NS4A protein of CSFV exhibited a potent VSR activity through binding to dsRNA and siRNA in the context of CSFV infection in mammalian cells, which are a conservative feature among . In addition, the replication of VSR-deficient CSFV was attenuated but could be restored by the deficiency of RNAi, providing a theoretical basis for the development of other important attenuated vaccines.
RNA 干扰（RNAi）是一种重要的转录后基因沉默机制，可作为真核生物的抗病毒免疫机制。然而，许多病毒可以通过编码病毒 RNA 沉默抑制剂（VSR）来逃避这种抗病毒 RNAi。经典猪瘟病毒（CSFV）属于瘟病毒属，是引起经典猪瘟（CSF）的病原体，对动物健康和养猪业有巨大影响。值得注意的是，目前对于 CSFV 如何在宿主中阻断 RNAi 知之甚少。在本文中，我们发现 CSFV NS4A 蛋白可以通过与双链 RNA 和小干扰 RNA 结合，在哺乳动物细胞中有效地拮抗 RNAi。此外，瘟病毒属中的 CSFV NS4A 具有 VSR 活性。此外，VSR 缺陷型 CSFV 的复制能力减弱，但在哺乳动物细胞中 RNAi 缺陷时可以恢复。总之，我们的研究揭示了 CSFV NS4A 是一种新型的 VSR，它可以在哺乳动物细胞中抑制 RNAi，并为我们深入了解 CSFV 和其他瘟病毒提供了新的视角。众所周知，RNAi 是一种重要的转录后基因沉默机制，也参与了哺乳动物细胞中的抗病毒反应。然而，许多病毒已经进化出通过编码 VSR 来阻断这种抗病毒免疫的能力。我们的数据表明，CSFV 的 NS4A 蛋白通过在哺乳动物细胞中结合 dsRNA 和 siRNA 表现出强大的 VSR 活性，这是瘟病毒属中的一个保守特征。此外，VSR 缺陷型 CSFV 的复制能力减弱，但通过 RNAi 缺陷可以恢复，这为开发其他重要的减毒疫苗提供了理论基础。
