Rottlerin plays an antiviral role at early and late steps of Zika virus infection

Shili Zhou; Quanshi Lin; Changbai Huang; Xiaotong Luo; Xu Tian; Chao Liu; Ping Zhang

doi:10.1016/j.virs.2022.07.012

October 2022

. doi: 10.1016/j.virs.2022.07.012

Citation: Shili Zhou, Quanshi Lin, Changbai Huang, Xiaotong Luo, Xu Tian, Chao Liu, Ping Zhang. Rottlerin plays an antiviral role at early and late steps of Zika virus infection .VIROLOGICA SINICA, 2022, 37(5) : 685-694. http://dx.doi.org/10.1016/j.virs.2022.07.012

楸毒素在寨卡病毒感染的早期和晚期发挥抗病毒作用

周诗丽 ^a,b ,
林泉士 ^a,c ,
黄常柏 ^a,c ,
罗晓彤 ^a,d ,
田旭 ^a,c ,
刘超 ^a,d,, ,
张萍 ^a,c,,

a 中山大学热带病防治重点实验室, 教育部, 广州, 510080;
b 广东省第二人民医院医学实验中心, 广州, 510317;
c 中山大学中山医学院免疫学系, 广州, 510080;
d 中山大学中山医学院微生物学系, 广州, 510080

通讯作者： 刘超, liuchao9@mail.sysu.edu.cn; 张萍, zhangp36@mail.sysu.edu.cn
收稿日期： 2022-03-12
录用日期： 2022-07-26

摘要

寨卡病毒感染可导致新生儿小头畸形和其他严重的神经系统疾病，目前尚无有效的疫苗和药物。本研究发现楸毒素对三种包膜病毒（包括寨卡病毒、水疱性口炎病毒、单纯疱疹病毒）具有抗病毒活性，但对两种裸病毒（肠道病毒71型、脑心肌炎病毒）无明显抑制作用；楸毒素对病毒粒子无直接杀伤作用，其抗病毒作用亦不依赖于其对PKCδ活性或ATP水平的调控。研究发现，楸毒素可抑制包膜病毒的内吞过程，并影响寨卡病毒粒子的成熟。在寨卡病毒感染的新生小鼠模型中，给予楸毒素可显著下调小鼠体内的病毒复制水平，并缓解寨卡病毒引起的神经症状。本研究表明楸毒素可在病毒感染的两个不同的阶段均发挥抗病毒作用，为其作为一个潜在的寨卡病毒防治药物提供理论依据。
- 寨卡病毒
- , 楸毒素
- , 包膜病毒
- , 复制

Rottlerin plays an antiviral role at early and late steps of Zika virus infection

Shili Zhou ^a,b ,
Quanshi Lin ^a,c ,
Changbai Huang ^a,c ,
Xiaotong Luo ^a,d ,
Xu Tian ^a,c ,
Chao Liu ^a,d,, ,
Ping Zhang ^a,c,,

a Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China;
b Medical Research Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China;
c Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China;
d Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

Corresponding author: Chao Liu, liuchao9@mail.sysu.edu.cn Ping Zhang, zhangp36@mail.sysu.edu.cn
Received Date: 12 March 2022
Accepted Date: 26 July 2022

Abstract

Infection of Zika virus (ZIKV) may cause microcephaly and other neurological disorders, while no vaccines and drugs are available. Our study revealed that rottlerin confers a broad antiviral activity against several enveloped viruses, including ZIKV, vesicular stomatitis virus, and herpes simplex virus, but not against two naked viruses (enterovirus 71 and encephalomyocarditis virus). Rottlerin does not have a direct virucidal effect on the virions, and its antiviral effect is independent of its regulation on PKCδ or ATP. Both pretreatment and post-treatment of rottlerin effectively reduce the viral replication of ZIKV. The pretreatment of rottlerin disturbs the endocytosis of enveloped viruses, while the post-treatment of rottlerin acts at a late stage through disturbing the maturation of ZIKV. Importantly, administration of rottlerin in neonatal mice significantly decreased the ZIKV replication in vivo, and alleviated the neurological symptoms caused by ZIKV. Our work suggests that rottlerin exerts an antiviral activity at two distinct steps of viral infection, and can be potentially developed as a prophylactic and therapeutic agent.
- Zika virus (ZIKV)
- , Rottlerin
- , Enveloped virus
- , Replication

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Electronic Supplementary Material

10.1016j.virs.2022.07.012-ESM.docx