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J Virol ; 98(6): e0170523, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38742902

RESUMO

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 AP2B1, CHMP4C, DNM1, FCHO1, and Src. Among them, loss of Src significantly decreases the uptake of ZIKV. Trans-complementation of Src in the LINC08148KO cells largely restores the caveola-mediated endocytosis of ZIKV, indicating that the proviral effect of LINC08148 is exerted through Src. Finally, LINC08148 upregulates the Src 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. IMPORTANCE: 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.


Assuntos
Endocitose , RNA Longo não Codificante , Internalização do Vírus , Infecção por Zika virus , Zika virus , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/genética , Zika virus/genética , Zika virus/fisiologia , Humanos , Infecção por Zika virus/virologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/genética , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp1/genética , Cavéolas/metabolismo , Animais , Replicação Viral , Regulação para Cima , Vírus da Dengue/fisiologia , Vírus da Dengue/genética , Chlorocebus aethiops , Células HEK293 , Células Vero , Quinases da Família src/metabolismo , Quinases da Família src/genética
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