Lnc-DARVR/miR-365-1-5p/LAMB1 axis regulates rotavirus replication via the complement C3 pathway

作者：Xiaopeng Song, Lida Yao, Yan Li, Jinlan Wang, Chenxing Lu, Jinmei Li, Qingmei Leng, Xianqiong Tang, Xiaoqing Hu, Jinyuan Wu, Rong Chen, Xiaochen Lin, Jun Ye, Xiangjun Kuang, Guangming Zhang, Maosheng Sun, Yan Zhou, Hongjun Li · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.02114-24 · 被引用次数：4 · 研究领域：Viral gastroenteritis research and epidemiology、Respiratory viral infections research、Virus-based gene therapy research

Antiviral effectors and cytokines are critical components of host innate immunity. However, the regulatory mechanisms governing the roles of these molecules in host-virus interactions are still unclear. Although long non-coding RNAs (lncRNAs) have been recognized as key players in various biological processes, their involvement in the complement system of host antiviral defenses remains to be explored. In this study, we discovered a novel, unannotated lncRNA, called DARVR. DARVR was found to be an intergenic lncRNA and inhibited rotavirus (RV) replication in MA104 cells. Mechanistically, we found that complement 3 (C3) was upregulated following RV infection in a LAMB1-dependent manner. However, LAMB1 expression was downregulated by miR-365-1-5p, resulting in the inhibition of the C3-mediated antiviral reaction. However, DARVR functioned as a competing endogenous RNA against miR-365-1-5p, promoting the expression of LAMB1 and thereby enhancing C3 activity and inhibiting RV replication. These results not only provide evidence demonstrating the involvement of lncRNAs in the regulation of RV infection but also highlight the role of complement factors in host innate immunity. IMPORTANCE: Long non-coding RNAs (lncRNAs) play versatile and critical roles in host-virus interactions, offering significant potential for developing targeted therapies to prevent or treat viral infections. Despite their importance, the involvement of lncRNAs in rotavirus infection remains underexplored. Thi...