Rottlerin plays an antiviral role at early and late steps of Zika virus infection.
Rottlerin plays an antiviral role at early and late steps of Zika virus infection.
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DOI：
10.1016/j.virs.2022.07.012
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发表时间：
2022-10
影响因子：
5.5
通讯作者：
Zhang, Ping
中科院分区：
文献类型：
--
作者：
Zhou, Shili;Lin, Quanshi;Tian, Xu;Liu, Chao;Zhang, Ping
寨卡病毒（ZIKV）感染可能会导致小头畸形和其他神经系统疾病，但目前尚无疫苗和药物可用。我们的研究表明，rottlerin 对多种包膜病毒具有广泛的抗病毒活性，包括 ZIKV、水泡性口炎病毒和单纯疱疹病毒，但对两种裸病毒（肠道病毒 71 和脑心肌炎病毒）没有作用。 Rottlerin 对病毒粒子没有直接的杀病毒作用，其抗病毒作用与其对 PKCδ 或 ATP 的调节无关。 Rottlerin的预处理和后处理均有效减少ZIKV的病毒复制。 Rottlerin 的预处理会干扰有包膜病毒的内吞作用，而 Rottlerin 的后处理则通过干扰 ZIKV 的成熟来在后期发挥作用。重要的是，给新生小鼠注射rottlerin可显着降低ZIKV在体内的复制，并减轻ZIKV引起的神经系统症状。我们的工作表明，rottlerin 在病毒感染的两个不同步骤中发挥抗病毒活性，并且有可能被开发为预防和治疗剂。 Rottlerin 对包括寨卡病毒在内的多种包膜病毒具有抗病毒活性。 Rottlerin 干扰寨卡病毒的内吞作用和成熟步骤。 Rottlerin 抑制 ZIKV 体内复制，缓解寨卡病毒引起的神经症状。
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. Rottlerin confers an antiviral activity against several enveloped viruses including Zika virus. Rottlerin interferes with the endocytosis and maturation step of Zika virus. Rottlerin inhibits the ZIKV replication in vivo, and alleviates the neurological symptoms caused by Zika virus.
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