Processing of Genomic RNAs by Dicer in Bat Cells Limits SARS-CoV-2 Replication

This project investigates the molecular responses of Tadarida brasiliensis (Brazilian free-tailed bat) cells to SARS-CoV-2 infection and Poly(I:C) treatment using both small RNA sequencing (small RNA-seq) and mRNA sequencing (RNA-seq). Through small RNA-seq, we analyzed the differential expression of small RNAs, including miRNAs, in uninfected and SARS-CoV-2-infected cells, uncovering key alterations in endogenous small RNA biogenesis pathways influenced by the virus. Additionally, we explored the role of Dicer in antiviral defense by comparing small RNA profiles in Dicer knockdown and control cells, revealing that Dicer facilitates the processing of viral RNAs into siRNA-like fragments, contributing to viral replication control. Using mRNA-seq, we examined the transcriptomic changes in bat cells during SARS-CoV-2 infection and Poly(I:C) treatment, focusing on differentially expressed genes and pathways involved in the immune response. These analyses identified critical genes and pathways associated with antiviral defense mechanisms, including dsRNA sensors and host immune regulators, providing comprehensive insights into how T. brasiliensis interacts with viral infections and dsRNA mimics at both the small RNA and mRNA levels. This integrative approach enhances our understanding of bat antiviral strategies and their unique regulatory RNA pathways.

本研究针对巴西游离尾蝠（Tadarida brasiliensis）细胞，分别采用小RNA测序（small RNA-seq）与mRNA测序（RNA-seq）技术，探究其在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染及Poly(I:C)处理后的分子应答反应。通过小RNA测序，本研究分析了未感染与SARS-CoV-2感染细胞中小RNA（包括微小RNA，miRNA）的差异表达情况，揭示了病毒影响的内源性小RNA生成通路的关键改变。此外，本研究通过对比Dicer基因敲低细胞与对照细胞的小RNA表达谱，探究了Dicer在抗病毒防御中的作用，发现Dicer可介导病毒RNA加工为小干扰RNA（siRNA）类似片段，从而参与病毒复制的调控过程。利用mRNA测序技术，本研究检测了巴西游离尾蝠细胞在SARS-CoV-2感染及Poly(I:C)处理后的转录组变化，重点聚焦于参与免疫应答的差异表达基因与通路。上述分析鉴定出与抗病毒防御机制相关的关键基因及通路，包括双链RNA（dsRNA）感受器及宿主免疫调控因子，全面阐明了巴西游离尾蝠在小RNA与mRNA层面与病毒感染及双链RNA模拟物的互作机制。本整合组学研究策略，加深了学界对蝙蝠抗病毒策略及其独特调控RNA通路的认知。