Lycorine provides antiviral activities against mandarin fish ranavirus via suppressing apoptosis and activating type I interferon pathway

文献类型： 外文期刊

第一作者： Jia, Mengyan

作者： Jia, Mengyan;Guo, Hui;Jia, Mengyan;Ma, Yanping;Hao, Le;Tao, Ziqian;Wang, Jingya;Liu, Zhenxing;Tao, Ziqian;Wang, Jingya;Liao, Sentai

作者机构：

关键词： MRV; Lycorine; Apoptosis; Interferon; ROS

期刊名称：AQUACULTURE （ 影响因子：3.9； 五年影响因子：4.4 ）

ISSN： 0044-8486

年卷期： 2025 年 598 卷

页码：

收录情况： SCI

摘要： Mandarin fish ranavirus (MRV), as an emerging iridescent virus spread rapidly in China. To develop new antiMRV strategies, in vitro and in vivo antiviral activities of lycorine were evaluated. In vitro, assays were conducted on mandarin fish brain-derived SCB3 cells. We found that lycorine exhibited therapeutic effect to prevent MRV replication, including the reduction of virus titters and suppression of MRV-MCP expression. Then, we sought to decipher the mechanisms underlying lycorine-mediated antiviral activities from the perspective of regulating apoptosis and type I interferon responses. JC-1 staining indicated that lycorine reversed the MRVtriggered collapse of MMP. Furthermore, lycorine defended the MRV-induced up-regulation of pro-apoptotic genes (Bad, Bax and p53) and down-regulation of anti-apoptotic genes (Bcl-2b, Bcl-xL and Mcl). As executor and initiator of apoptosis, caspase-3 and caspase-8 activities were inhibited by lycorine. Moreover, lycorine extinguished MRV-stimulated ROS to normal level. These founding argued that lycorine exerted the anti-MRV activities by regulating the mitochondrial apoptosis pathway. Subsequently, we confirmed that the expression of type I interferon pathway-related genes were activated by lycorine, which provided extra explanations to understand its anti-MRV mechanisms. In vivo assays, gavage administration of lycorine at doses above 19 mg/kg increased the survival rate of MRV-challenged mandarin fish from 20.00 % to 52.00 %, alongside with the reduction of MRV loads in spleen and head kidney. In addition, the activation of anti-apoptosis genes versus inhibition of pro-apoptosis genes was also found in the lycorine-treated fish. Overall, our study ascertained the activities of lycorine against MRV infection and provided new insights for discovering anti-MRV drugs.

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