鱼类特有microRNA miR-462/731簇调控细胞自噬抑制神经坏死病毒感染的分子机制

细胞自噬作为宿主免疫系统的重要组成部分，在神经坏死病毒（NNV）感染中被病毒劫持，促进其增殖。但宿主如何抑制NNV诱导的细胞自噬尚不清楚。miRNA可以通过调控自噬相关基因及其调控因子影响自噬发生。在前期研究中，我们发现NNV感染诱导鱼类特有miRNA miR-462/731表达，且过表达miR-462/731抑制NNV复制及NNV诱导的自噬。进一步研究发现自噬信号通路关键基因BECN1和ULK1分别是miR-462和miR-731的潜在靶基因，推测miR-462/731可能通过负调控自噬信号通路进而抑制NNV感染，但其具体分子机制有待阐明。本项目拟继续研究miR-462/731与自噬及NNV感染的相关性，明确它们的靶基因及其功能，阐明miR-462和miR-731协同调控自噬抑制NNV感染的分子机制。本研究将有助于理解鱼类具有自身特点的抗病毒机制，为NNV防控技术开发提供理论依据。

Nervous necrosis virus (NNV) is a highly infectious and harmful fish pathogen and seriously affects the development of aquaculture in China. Autophagy, as an important part of the host immune system, is hijacked by NNV and promotes its proliferation. However, it remains unclear how the host inhibits NNV-induced autophagy. MicroRNA (miRNA) can affect autophagy by regulating autophagy related genes and their regulators. Our preliminary studies indicated that fish-specific miRNAs miR-462/731 were significantly unregulated by NNV infection, and overexpression of miR-462/731 inhibited NNV replication and NNV-induced autophagy. Further studies showed that BECN1 and ULK1, key genes of autophagy signaling pathway, were potential targets of miR-462 and miR-731, respectively. Thus we speculated that miR-462/731 may inhibit NNV infection by negatively regulating autophagy signaling pathway, but its molecular mechanism remains to be elucidated. This project intends to continue to study the relationship between miR-462/731, autophagy and NNV infection, clarify target genes of miR-462/731, and elucidate the molecular mechanism of miR-462 and miR-731 co-regulating autophagy and inhibiting NNV infection. These results will aid to understand fish-own antiviral mechanisms mediated by fish-specific miRNAs miR-462/731, and provide a theoretical basis for the development of NNV prevention and control technology.