Host Cellular RNA Helicases Regulate SARS-CoV-2 Infection.
Host Cellular RNA Helicases Regulate SARS-CoV-2 Infection.
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DOI：
10.1128/jvi.00002-22
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发表时间：
2022-03-23
影响因子：
5.4
通讯作者：
Ariumi Y
中科院分区：
文献类型：
--
作者：
Ariumi Y
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是RNA病毒中RNA基因组最大的病毒，约30 kb。DDX DEAD box 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解旋酶可以调节和维持如此大的病毒RNA基因组。在这项研究中，我调查了几种宿主细胞RNA解旋酶在SARS-CoV-2感染中的潜在作用。值得注意的是，DDX 21敲低显著积累细胞内病毒RNA和病毒产生，以及SARS-CoV-2的病毒感染性，表明DDX 21强烈限制SARS-CoV-2感染。此外，MOV 10 RNA解旋酶还能抑制SARS-CoV-2的感染。相反，DDX 1、DDX 5和DDX 6 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DDX 6和MOV 10 RNA解旋酶以及XRN 1外切核酸酶的P体形成，而病毒感染并不诱导应激颗粒形成。因此，SARS-CoV-2核衣壳（N）蛋白与DDX 1、DDX 3、DDX 5、DDX 6、DDX 21和MOV 10相互作用并破坏P体形成，表明SARS-CoV-2 N劫持DDX 6进行病毒复制。相反，DDX 21和MOV 10通过SARS-CoV-2 N与宿主细胞RNA解旋酶的相互作用来限制SARS-CoV-2感染。总之，宿主细胞RNA解旋酶似乎调节SARS-CoV-2感染。重要信息SARS-CoV-2具有约30 kb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复制。在这项研究中，我已经证明DDX 21和MOV 10 RNA解旋酶限制病毒感染和复制。相反，DDX 1、DDX 5和DDX 6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，减弱或抑制了应激颗粒的形成。因此，SARS-CoV-2似乎劫持宿主细胞RNA解旋酶，通过促进病毒感染和复制以及抑制宿主先天免疫系统来发挥前病毒作用。
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. IMPORTANCE 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.
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影响因子：
14.9
作者：
Fuller-Pace FV
通讯作者：
Fuller-Pace FV
影响因子：
30.3
作者：
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影响因子：
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