A novel IFNbeta-induced long non-coding RNA ZAP-IT1 interrupts Zika virus replication in A549 cells

Yanxia Huang; Yu Su; Li Shen; Zhiting Huo; Cancan Chen; Tao Sun; Xu Tian; Ning Li; Chao Yang

doi:10.1016/j.virs.2022.08.003

December 2022

. doi: 10.1016/j.virs.2022.08.003

Citation: Yanxia Huang, Yu Su, Li Shen, Zhiting Huo, Cancan Chen, Tao Sun, Xu Tian, Ning Li, Chao Yang. A novel IFNbeta-induced long non-coding RNA ZAP-IT1 interrupts Zika virus replication in A549 cells .VIROLOGICA SINICA, 2022, 37(6) : 904-912. http://dx.doi.org/10.1016/j.virs.2022.08.003

一种新的干扰素诱导的长非编码RNA ZAP-IT1阻断寨卡病毒在A549细胞中的复制

黄燕霞 ^a ,
苏煜 ^a ,
沈莉 ^b ,
霍志婷 ^c ,
陈灿灿 ^d ,
孙韬 ^a ,
田旭 ^c ,
李宁 ^a ,
杨超 ^a,,

中山大学附属第一医院神经外科;中山大学中山医学院微生物教研室;中山大学中山医学院免疫学教研室;中山大学附属第一医院病理科

通讯作者： 杨超, ychao@mail.sysu.edu.cn
收稿日期： 2021-12-29
录用日期： 2022-08-09

摘要

寨卡病毒（Zika virus，ZIKV）感染可导致严重的神经系统疾病，包括新生儿小头畸形和格林-巴利综合征。长非编码RNA（lncRNAs）是转录过程的副产物，可能参与病毒的感染过程。然而，宿主lncRNAs是否在ZIKV感染中起作用，在很大程度上尚不清楚。本研究鉴定了一组在ZIKV感染后上调并依赖于I型干扰素（IFN）信号的人lncRNAs。lncRNA ZAP-IT1的过表达可显著下调ZIKV的感染。而敲除ZAP-IT1则使得ZIKV的感染增强。ZAP-IT1是一种内含子型lncRNA，长度为551nt，主要分布于细胞核内。ZAP-IT1还具有抵抗登革病毒（DENV）、日本脑炎病毒（JEV）或水泡性口炎病毒（VSV）感染的作用。在机制方面，本研究发现ZAP-IT1的抗病毒作用独立于I型干扰素信号通路。综上，本研究揭示了由I型IFN信号诱导的宿主lncRNA ZAP-IT1，具有抑制ZIKV感染、甚至DENV、JEV和VSV感染的作用，这可能有助于抗病毒治疗的发展。
- 寨卡病毒(ZIKV)
- , 长链非编码RNA (lncRNA)
- , 干扰素刺激基因(ISG)
- , 限制因子
- , 病毒复制

A novel IFNbeta-induced long non-coding RNA ZAP-IT1 interrupts Zika virus replication in A549 cells

Yanxia Huang ^a ,
Yu Su ^a ,
Li Shen ^b ,
Zhiting Huo ^c ,
Cancan Chen ^d ,
Tao Sun ^a ,
Xu Tian ^c ,
Ning Li ^a ,
Chao Yang ^a,,

a Department of Neurosurgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China;

Corresponding author: Chao Yang, ychao@mail.sysu.edu.cn
Received Date: 29 December 2021
Accepted Date: 09 August 2022

Abstract

Zika virus (ZIKV) infection can cause severe neurological diseases including neonatal microcephaly and Guillain-Barre syndrome. Long noncoding RNAs (lncRNAs) are the by-products of the transcription process, which are considered to affect viral infection. However, it remains largely unexplored whether host lncRNAs play a role in ZIKV infection. Here, we identified a group of human lncRNAs that were up-regulated upon ZIKV infection and were dependent on the type I interferon (IFN) signaling. Overexpression of lncRNA ZAP-IT1 leads to an impairment of ZIKV infection. Correspondently, deficiency of ZAP-IT1 led to an enhancement of ZIKV infection. We further confirmed that ZAP-IT1, an intronic lncRNA with total 551 nt in length, is mainly located in the nuclear upon ZIKV infection. Knockout of ZAP-IT1 also led to the increase of dengue virus (DENV), Japanese encephalitis virus (JEV), or vesicular stomatitis virus (VSV) infection. Mechanically, we found that the antiviral effect of ZAP-IT1 was independent of the type I IFN signaling pathway. Therefore, our data unveiled that host lncRNA ZAP-IT1 induced by the type I IFN signaling, showed robust restriction on ZIKV infection, and even on DENV, JEV, and VSV infection, which may benefit the development of antiviral therapeutics.
- Zika virus (ZIKV)
- , Long noncoding RNA (lncRNA)
- , Interferon-stimulated gene (ISG)
- , Restriction factor
- , Viral replication

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Electronic Supplementary Material

10.1016j.virs.2022.08.003-ESM.docx