LINC08148 promotes the caveola-mediated endocytosis of Zika virus through upregulating transcription of Src

• Published in: Journal of virology 2024-06, Vol.98 (6), p.e0170523
• Main Authors: Huo, Zhiting, Zhu, Xuanfeng, Peng, Qinyu, Chen, Cancan, Yang, Xiaoyi, Huang, Changbai, Xiang, Yincheng, Tian, Qingju, Liu, Jingyu, Liu, Chao, Zhang, Ping
• Format: Article
• Language: English
• Subjects: Animals; Caveolae - metabolism; Chlorocebus aethiops; Dengue Virus - genetics; Dengue Virus - physiology; Endocytosis; HEK293 Cells; Humans; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; src-Family Kinases - genetics; src-Family Kinases - metabolism; Up-Regulation; Vero Cells; Virology; Virus Internalization; Virus Replication; Virus-Cell Interactions; Zika Virus - genetics; Zika Virus - physiology; Zika Virus Infection - genetics; Zika Virus Infection - metabolism; Zika Virus Infection - virology
• ISSN: 0022-538X; 1098-5514; 1098-5514
• DOI: 10.1128/jvi.01705-23

Long non-coding RNAs (lncRNAs) represent a new group of host factors involved in viral infection. Current study identified an intergenic lncRNA, LINC08148, as a proviral factor of Zika virus (ZIKV) and Dengue virus 2 (DENV2). Knockout (KO) or silencing of LINC08148 decreases the replication of ZIKV and DENV2. LINC08148 mainly acts at the endocytosis step of ZIKV but at a later stage of DENV2. RNA-seq analysis reveals that LINC08148 knockout downregulates the transcription levels of five endocytosis-related genes including , , , , and . Among them, loss of Src significantly decreases the uptake of ZIKV. -complementation of Src in the LINC08148 cells largely restores the caveola-mediated endocytosis of ZIKV, indicating that the proviral effect of LINC08148 is exerted through Src. Finally, LINC08148 upregulates the transcription through associating with its transcription factor SP1. This work establishes an essential role of LINC08148 in the ZIKV entry, underscoring a significance of lncRNAs in the viral infection. Long non-coding RNAs (lncRNAs), like proteins, participate in viral infection. However, functions of most lncRNAs remain unknown. In this study, we performed a functional screen based on microarray data and identified a new proviral lncRNA, LINC08148. Then, we uncovered that LINC08148 is involved in the caveola-mediated endocytosis of ZIKV, rather than the classical clathrin-mediated endocytosis. Mechanistically, LINC08148 upregulates the transcription of Src, an initiator of caveola-mediated endocytosis, through binding to its transcription factor SP1. This study identifies a new lncRNA involved in the ZIKV infection, suggesting lncRNAs and cellular proteins are closely linked and cooperate to regulate viral infection.