State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Cell Rep. 2024 Aug 27;43(8):114581. doi: 10.1016/j.celrep.2024.114581. Epub 2024 Aug 4.
Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigate the antiviral RNA interference pathway in bat cells and discover that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs upon Sindbis virus infection that are missing in human cells. Disruption of Dicer function results in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors, such as retinoic acid-inducible gene I, with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.
蝙蝠携带高度致命的病毒，这些病毒可以感染其他哺乳动物，包括人类，这引发了关于它们免疫耐受机制的问题。蝙蝠细胞采用多种策略来限制病毒复制和病毒引起的免疫病理，但蝙蝠和致命病毒共存的情况仍知之甚少。在这里，我们研究了蝙蝠细胞中的抗病毒 RNA 干扰途径，发现它们具有增强的抗病毒 RNAi 反应，在感染辛德毕斯病毒后产生缺失于人类细胞中的典型病毒小干扰 RNA。干扰 Dicer 功能会导致三种不同的 RNA 病毒在蝙蝠细胞中的病毒载量增加，表明这是一种干扰素非依赖的抗病毒途径。此外，我们的研究结果揭示了 Dicer 与模式识别受体（如视黄酸诱导基因 I）与双链 RNA 的同时结合，表明 Dicer 减弱了蝙蝠细胞中干扰素反应的起始。这些发现增进了我们对蝙蝠与病毒共存所采用的独特策略的理解。
