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阿昔洛韦抑制虹鳟鱼病毒复制并保护虹鳟鱼卵巢细胞免于凋亡。

Acyclovir inhibits channel catfish virus replication and protects channel catfish ovary cells from apoptosis.

机构信息

College of Oceanography, Hohai University, Nanjing, 210098, China.

Jiangsu Agri-animal Husbandry Vocational College, China.

出版信息

Virus Res. 2021 Jan 15;292:198249. doi: 10.1016/j.virusres.2020.198249. Epub 2020 Nov 27.

Abstract

The channel catfish virus (CCV) can cause lethal hemorrhagic infection in channel catfish, resulting in significant economic losses in the fish industry. Effective drugs for the virus are still lacking. Acyclovir is known as a potent antiviral agent against human herpes viruses and some animal DNA viruses. The present study was undertaken to explore the antiviral response and mechanism of acyclovir against CCV in channel catfish ovary (CCO) cells. Acyclovir was able to significantly inhibit the expression of viral genes related to CCV viral DNA synthesis and suppress viral replication at a safe concentration. Furthermore, acyclovir blocked the cytopathic effects and apoptosis induced by CCV, thereby maintaining the normal cellular morphological structure, as shown by the protection of CCO cells from the formation of apoptotic bodies or nuclear fragmentation. Moreover, reverse transcript quantitative polymerase chain reaction (RT-qPCR) demonstrated that acyclovir suppressed the expression of caspase 3, caspase 8 and caspase 9, while there was no significant impact on the expression of the apoptosis-inhibiting gene bcl-2 in CCV-infected cells. In addition, acyclovir did not promote the expression of immune-related genes such as MyD88, Mx1, IRF3, IRF7, IFN-I, NF-kB and IL-1β, suggesting that the antiviral activity of acyclovir to CCV infection is not achieved by facilitating the expression of immune-related genes in CCO cells. Taken together, the results from this study suggest that acyclovir could effectively regulate CCV-induced infection, and thus is a promising therapeutic agent against CCV. Our results will aid our understanding of the pharmacological mechanisms of antiviral agents.

摘要

虹鳟鱼病毒(CCV)可引起虹鳟鱼致命性出血性感染,给鱼类养殖业造成重大经济损失。目前仍缺乏有效的针对该病毒的药物。阿昔洛韦是一种针对人类疱疹病毒和某些动物 DNA 病毒的有效抗病毒药物。本研究旨在探讨阿昔洛韦在虹鳟鱼卵巢(CCO)细胞中对 CCV 的抗病毒作用及其机制。结果表明,阿昔洛韦能在安全浓度下显著抑制与 CCV 病毒 DNA 合成相关的病毒基因表达,抑制病毒复制。此外,阿昔洛韦还能阻断 CCV 诱导的细胞病变效应和细胞凋亡,从而维持细胞正常形态结构,防止 CCO 细胞形成凋亡小体或核碎裂。实时定量 PCR(RT-qPCR)结果显示,阿昔洛韦抑制了 CCV 感染细胞中 caspase 3、caspase 8 和 caspase 9 的表达,但对凋亡抑制基因 bcl-2 的表达没有显著影响。此外,阿昔洛韦不会促进 MyD88、Mx1、IRF3、IRF7、IFN-I、NF-kB 和 IL-1β 等免疫相关基因的表达,表明阿昔洛韦对 CCV 感染的抗病毒活性并非通过促进 CCO 细胞中免疫相关基因的表达来实现。综上所述,本研究结果表明,阿昔洛韦可有效调节 CCV 诱导的感染,有望成为治疗 CCV 的潜在药物。该研究结果将有助于我们理解抗病毒药物的药理学机制。

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