Processing of genomic RNAs by Dicer in bat cells limits SARS-CoV-2 replication.

IF 4 3区 医学 Q2 VIROLOGY Virology Journal Pub Date : 2025-03-25 DOI:10.1186/s12985-025-02693-y
Iyanuoluwani J Owolabi, Shazeed-Ul Karim, Sweta Khanal, Sergio Valdivia, Christopher Frenzel, Fengwei Bai, Alex S Flynt
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Abstract

Bats are reservoirs for numerous viruses that cause serious diseases in other animals and humans. Several mechanisms are proposed to contribute to the tolerance of bats to these pathogens. This study investigates the response of bat cells to double-stranded RNA generated by SARS-CoV-2 replication. Here, we found the involvement of Dicer in the processing of viral genomic RNAs during SARS-CoV-2 infection. Examining RNA sequencing of infected cells, small-interfering RNA (siRNA)-like fragments were found derived from viral RNAs. Depletion of Dicer showed a reduction in these RNAs and an increase in viral loads suggesting unlike other mammals, bats may use Dicer to limit viral replication. This prompted the exploration of key dsRNA sensors in bat cells. Our analysis showed significant upregulation of OAS1 and MX1 in response to dsRNA, while PKR levels remained low, suggesting alternative dsRNA-response mechanisms are present that eschew the common PKR-based system. These results further show how bats employ distinct strategies for antiviral defense that may contribute to tolerating viral infections. They suggest the involvement of Dicer in antiviral mechanisms in bats, a function not observed in other mammals. This highlights a mechanism for bat originating viruses to evolve features that in other animals could cause extreme antiviral responses such as is seen with SARS-CoV-2.

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Dicer在蝙蝠细胞中加工基因组rna限制了SARS-CoV-2的复制。
蝙蝠是许多病毒的宿主,这些病毒在其他动物和人类中引起严重疾病。提出了几种机制来促进蝙蝠对这些病原体的耐受性。本研究探讨了蝙蝠细胞对SARS-CoV-2复制产生的双链RNA的反应。在这里,我们发现Dicer参与了SARS-CoV-2感染期间病毒基因组rna的加工。检查受感染细胞的RNA测序,发现来自病毒RNA的小干扰RNA (siRNA)样片段。Dicer的消耗显示这些rna的减少和病毒载量的增加,这表明与其他哺乳动物不同,蝙蝠可能使用Dicer来限制病毒复制。这促使人们探索蝙蝠细胞中关键的dsRNA传感器。我们的分析显示,OAS1和MX1在dsRNA的作用下显著上调,而PKR水平仍然很低,这表明存在替代的dsRNA反应机制,可以避开常见的基于PKR的系统。这些结果进一步表明蝙蝠如何采用不同的抗病毒防御策略,这可能有助于耐受病毒感染。他们认为Dicer参与了蝙蝠的抗病毒机制,这在其他哺乳动物中没有观察到。这突出了蝙蝠起源病毒进化特征的机制,这些特征在其他动物中可能引起极端的抗病毒反应,例如在SARS-CoV-2中看到的。
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来源期刊
Virology Journal
Virology Journal 医学-病毒学
CiteScore
7.40
自引率
2.10%
发文量
186
审稿时长
1 months
期刊介绍: Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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