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.

鲶鱼病毒（CCV）可导致鲶鱼发生致命的出血性感染，给渔业造成重大经济损失。目前仍缺乏针对该病毒的有效药物。阿昔洛韦被认为是一种有效的抗病毒剂，可以对抗人类疱疹病毒和一些动物 DNA 病毒。本研究旨在探讨阿昔洛韦对鲶鱼卵巢 (CCO) 细胞中 CCV 的抗病毒反应和机制。阿昔洛韦能够显着抑制与CCV病毒DNA合成相关的病毒基因的表达，并在安全浓度下抑制病毒复制。此外，阿昔洛韦阻断了CCV诱导的细胞病变和细胞凋亡，从而维持了正常的细胞形态结构，如保护 CCO 细胞免于形成凋亡小体或核碎裂所示。此外，逆转录定量聚合酶链反应 (RT-qPCR) 表明阿昔洛韦抑制了caspase 3、caspase 8和caspase 9，而对CCV感染细胞中凋亡抑制基因bcl-2的表达没有显着影响。此外，阿昔洛韦不促进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 感染的抗病毒活性不是通过促进 CCO 细胞中免疫相关基因的表达来实现的。总之，这项研究的结果表明阿昔洛韦可以有效调节 CCV 诱导的感染，因此是一种很有前途的 CCV 治疗剂。我们的结果将有助于我们了解抗病毒药物的药理机制。