Division of Retroelement, Joint Research Center for Human Retrovirus Infection, Kumamoto Universitygrid.274841.c, Kumamoto, Japan.
J Virol. 2022 Mar 23;96(6):e0000222. doi: 10.1128/jvi.00002-22. Epub 2022 Feb 2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the largest RNA genome, approximately 30 kb, among RNA viruses. The DDX DEAD box RNA helicase is a multifunctional protein involved in all aspects of RNA metabolism. Therefore, host RNA helicases may regulate and maintain such a large viral RNA genome. In this study, I investigated the potential role of several host cellular RNA helicases in SARS-CoV-2 infection. Notably, DDX21 knockdown markedly accumulated intracellular viral RNA and viral production, as well as viral infectivity of SARS-CoV-2, indicating that DDX21 strongly restricts the SARS-CoV-2 infection. In addition, MOV10 RNA helicase also suppressed the SARS-CoV-2 infection. In contrast, DDX1, DDX5, and DDX6 RNA helicases were required for SARS-CoV-2 replication. Indeed, SARS-CoV-2 infection dispersed the P-body formation of DDX6 and MOV10 RNA helicases as well as XRN1 exonuclease, while the viral infection did not induce stress granule formation. Accordingly, the SARS-CoV-2 nucleocapsid (N) protein interacted with DDX1, DDX3, DDX5, DDX6, DDX21, and MOV10 and disrupted the P-body formation, suggesting that SARS-CoV-2 N hijacks DDX6 to carry out viral replication. Conversely, DDX21 and MOV10 restricted SARS-CoV-2 infection through an interaction of SARS-CoV-2 N with host cellular RNA helicases. Altogether, host cellular RNA helicases seem to regulate the SARS-CoV-2 infection. SARS-CoV-2 has a large RNA genome, of approximately 30 kb. To regulate and maintain such a large viral RNA genome, host RNA helicases may be involved in SARS-CoV-2 replication. In this study, I have demonstrated that DDX21 and MOV10 RNA helicases limit viral infection and replication. In contrast, DDX1, DDX5, and DDX6 are required for SARS-CoV-2 infection. Interestingly, SARS-CoV-2 infection disrupted P-body formation and attenuated or suppressed stress granule formation. Thus, SARS-CoV-2 seems to hijack host cellular RNA helicases to play a proviral role by facilitating viral infection and replication and by suppressing the host innate immune system.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的 RNA 基因组是 RNA 病毒中最大的，约 30kb。DDX DEAD 框 RNA 解旋酶是一种多功能蛋白，参与 RNA 代谢的各个方面。因此，宿主 RNA 解旋酶可能调节和维持如此大的病毒 RNA 基因组。在这项研究中，我研究了几种宿主细胞 RNA 解旋酶在 SARS-CoV-2 感染中的潜在作用。值得注意的是，DDX21 的敲低显著积累了细胞内病毒 RNA 和病毒产生，以及 SARS-CoV-2 的病毒感染力，表明 DDX21 强烈限制了 SARS-CoV-2 的感染。此外，MOV10 RNA 解旋酶也抑制了 SARS-CoV-2 的感染。相比之下，DDX1、DDX5 和 DDX6 RNA 解旋酶是 SARS-CoV-2 复制所必需的。事实上，SARS-CoV-2 感染分散了 DDX6 和 MOV10 RNA 解旋酶以及 XRN1 外切酶的 P 体形成，而病毒感染并未诱导应激颗粒形成。因此，SARS-CoV-2 核衣壳（N）蛋白与 DDX1、DDX3、DDX5、DDX6、DDX21 和 MOV10 相互作用并破坏 P 体形成，表明 SARS-CoV-2 N 劫持 DDX6 以进行病毒复制。相反，DDX21 和 MOV10 通过 SARS-CoV-2 N 与宿主细胞 RNA 解旋酶的相互作用限制了 SARS-CoV-2 的感染。总之，宿主细胞 RNA 解旋酶似乎调节 SARS-CoV-2 的感染。SARS-CoV-2 具有约 30kb 的大 RNA 基因组。为了调节和维持如此大的病毒 RNA 基因组，宿主 RNA 解旋酶可能参与 SARS-CoV-2 的复制。在这项研究中，我已经证明 DDX21 和 MOV10 RNA 解旋酶限制病毒感染和复制。相反，DDX1、DDX5 和 DDX6 是 SARS-CoV-2 感染所必需的。有趣的是，SARS-CoV-2 感染破坏了 P 体的形成，并减弱或抑制了应激颗粒的形成。因此，SARS-CoV-2 似乎通过促进病毒感染和复制以及抑制宿主固有免疫系统来劫持宿主细胞 RNA 解旋酶发挥助病毒作用。
