Increased viral tolerance mediates by antiviral RNA interference in bat cells
Yunpeng Dai,
Binbin Wang,
Jiaxin Wang,
Xiaocui Wei,
Xing Liu,
Xu Che,
Junxia Li,
Wei Lun Ng,
Lin-Fa Wang,
Yang Li
Affiliations
Yunpeng Dai
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
Binbin Wang
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
Jiaxin Wang
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
Xiaocui Wei
CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Xing Liu
CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Xu Che
CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Junxia Li
CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Wei Lun Ng
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore
Lin-Fa Wang
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore
Yang Li
CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Corresponding author
Summary: 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.
