Owolabi Iyanuoluwani J, Karim Shazeed-Ul, Khanal Sweta, Valdivia Sergio, Frenzel Christopher, Bai Fengwei, Flynt Alex S
Cellular and Molecular Biology, University of Southern Mississippi, Hattiesburg, MS, 39406, USA.
Virol J. 2025 Mar 25;22(1):86. doi: 10.1186/s12985-025-02693-y.
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.
蝙蝠是多种病毒的宿主，这些病毒可在其他动物和人类中引发严重疾病。人们提出了几种机制来解释蝙蝠对这些病原体的耐受性。本研究调查了蝙蝠细胞对由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）复制产生的双链RNA的反应。在此，我们发现了Dicer在SARS-CoV-2感染期间参与病毒基因组RNA的加工过程。通过检查受感染细胞的RNA测序，发现了源自病毒RNA的小干扰RNA（siRNA）样片段。Dicer的缺失导致这些RNA减少且病毒载量增加，这表明与其他哺乳动物不同，蝙蝠可能利用Dicer来限制病毒复制。这促使我们探索蝙蝠细胞中的关键双链RNA传感器。我们的分析表明，响应双链RNA时，2'-5'-寡腺苷酸合成酶1（OAS1）和Mx蛋白1（MX1）显著上调，而蛋白激酶R（PKR）水平保持较低，这表明存在替代的双链RNA反应机制，避开了常见的基于PKR的系统。这些结果进一步表明蝙蝠如何采用独特的抗病毒防御策略，这可能有助于它们耐受病毒感染。它们表明Dicer参与了蝙蝠的抗病毒机制，这一功能在其他哺乳动物中未观察到。这突出了一种机制，即源自蝙蝠的病毒如何进化出在其他动物中可能引发极端抗病毒反应的特征，如在SARS-CoV-2中所见。
