Academic Journal
In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection
| العنوان: | In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection |
|---|---|
| المؤلفون: | Chen, Xingjuan, Yan, Yunzheng, Liu, Zhiqiang, Yang, Shaokang, Li, Wei, Wang, Zhuang, Wang, Mengyuan, Guo, Juan, Li, Zhenyang, Zhu, Weiyan, Yang, Jingjing, Yin, Jiye, Dai, Qingsong, Li, Yuexiang, Wang, Cui, Zhao, Lei, Yang, Xiaotong, Guo, Xiaojia, Leng, Ling, Xu, Jiaxi, Obukhov, Alexander G., Cao, Ruiyuan, Zhong, Wu |
| المساهمون: | Anatomy, Cell Biology and Physiology, School of Medicine |
| المصدر: | PMC |
| بيانات النشر: | EMBO Press |
| سنة النشر: | 2024 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | Zika virus, TRPC4 channel, Calcium, Epilepsy, Antiviral target |
| الوصف: | Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | EMBO Molecular Medicine; https://hdl.handle.net/1805/43863 |
| الاتاحة: | https://hdl.handle.net/1805/43863 |
| Rights: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.ACC14023 |
| قاعدة البيانات: | BASE |
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