Unfolding of an RNA G-quadruplex motif in the negative strand genome of porcine reproductive and respiratory syndrome virus by host and viral helicases to promote viral replication

文献类型： 外文期刊

第一作者： Fang, Puxian

作者： Fang, Puxian;Xie, Congbao;Pan, Ting;Cheng, Ting;Chen, Wei;Xia, Sijin;Ding, Tong;Fang, Junkang;Zhou, Yanrong;Fang, Liurong;Wei, Dengguo;Xiao, Shaobo;Fang, Puxian;Pan, Ting;Cheng, Ting;Chen, Wei;Xia, Sijin;Ding, Tong;Zhou, Yanrong;Fang, Liurong;Xiao, Shaobo;Xie, Congbao;Fang, Junkang;Wei, Dengguo;Xie, Congbao;Fang, Junkang;Wei, Dengguo;Xie, Congbao;Fang, Junkang;Wei, Dengguo;Xie, Congbao;Fang, Junkang;Wei, Dengguo

作者机构：

期刊名称：NUCLEIC ACIDS RESEARCH （ 影响因子：14.9； 五年影响因子：16.4 ）

ISSN： 0305-1048

年卷期： 2023 年 51 卷 19 期

页码：

收录情况： SCI

摘要： G-quadruplex (G4) is a unique secondary structure formed by guanine-rich nucleic acid sequences. Growing studies reported that the genomes of some viruses harbor G4 structures associated with viral replication, opening up a new field to dissect viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV), a representative member of Arteriviridae, is an economically significant pathogen that has devastated the swine industry worldwide for over 30 years. In this study, we identified a highly conserved G-rich sequence with parallel-type G4 structure (named PRRSV-G4) in the negative strand genome RNA of PRRSV. Pyridostatin (PDS), a well-known G4-binding ligand, stabilized the PRRSV-G4 structure and inhibited viral replication. By screening the proteins interacting with PRRSV-G4 in PRRSV-infected cells and single-molecule magnetic tweezers analysis, we found that two helicases, host DDX18 and viral nsp10, interact with and efficiently unwound the PRRSV-G4 structure, thereby facilitating viral replication. Using a PRRSV reverse genetics system, we confirmed that recombinant PRRSV with a G4-disruptive mutation exhibited resistance to PDS treatment, thereby displaying higher replication than wild-type PRRSV. Collectively, these results demonstrate that the PRRSV-G4 structure plays a crucial regulatory role in viral replication, and targeting this structure represents a promising strategy for antiviral therapies. Graphical Abstract

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