trifloxystrobin and Virus-Diseases

Chronic pollution in aquatic ecosystems can lead to many adverse effects, including a greater susceptibility to pathogens among resident biota. Trifloxystrobin (TFS) is a strobilurin fungicide widely used in Asia to control soybean rust. However, it has the potential to enter aquatic ecosystems, where it may impair fish resistance to viral infections. To explore the potential environmental risks of TFS, we characterized the antiviral capacities of fish chronically exposed to TFS and subsequently infected with spring viraemia of carp virus (SVCV). Although TFS exhibited no significant cytotoxicity at the tested environmental concentrations during viral challenge, SVCV replication increased significantly in a time-dependent manner within epithelioma papulosum cyprini (EPC) cells and zebrafish exposed to 25 μg/L TFS. Results showed that the highest viral load was more than 100-fold that of the controls. Intracellular biochemical assays indicated that autophagy was induced by TFS, and associated changes included an increase in autophagosomes, conversion of LC3-II, accumulation of Beclin-1, and degradation of P62 in EPC cells and zebrafish. In addition, TFS markedly decreased the expression and phosphorylation of mTOR, indicating that activation of TFS may be associated with the mTOR-mediated autophagy pathway. This study provides new insights into the mechanism of the immunosuppressive effects of TFS on non-target aquatic hosts and suggests that the existence of TFS in aquatic environments may contribute to outbreaks of viral diseases.. 水生生态系统中存在的长期污染会对水生环境以及水生生物产生多种不利影响，其中包括提高水生生物对病原体的敏感性。肟菌酯（TFS）是一种在亚洲广泛用于防治大豆锈病的甲氧基丙烯酸酯类农药。然而，在长期使用的过程中它有可能进入并污染水生生态系统导致鱼类对病毒抵抗力降低。为了研究TFS潜在的水环境风险，我们检测了长期暴露于TFS的宿主在鲤春病毒血症病毒（spring viraemia of carp virus，SVCV）感染下抗病能力的变化。实验结果表明，尽管环境浓度25 μg/L暴露下的TFS对细胞和斑马鱼没有明显毒性，但SVCV增殖却随着暴露时间的增长显著增加，最高病毒载量甚至相对于对照组呈现100倍以上的增加。先前的研究表明，鱼类出现自噬将有利于SVCV在机体内增殖。而我们则发现，长时间TFS暴露下的EPC细胞和斑马鱼出现自噬体增加、LC3蛋白转化、Beclin-1累积、P62蛋白降解及mTOR表达和磷酸化水平下降，这些说明TFS通过诱导宿主自噬提高宿主的病毒易感性。综上所述，该研究提出了TFS对非靶标水生生物致毒机制的新见解，提醒我们应关注甲氧基类农药在水环境中蓄积可能会诱发鱼类病毒病暴发，从而危及生态环境的安全。.

Topics: Acetates; Animals; Autophagy; Disease Susceptibility; Fungicides, Industrial; Imines; Strobilurins; Virus Diseases; Water Pollutants, Chemical; Zebrafish