Abstract：
The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broad-spectrum antiviral activity. However, some viruses hijack MARCH8 to promote virus replication, highlighting its dual role in the viral lifecycle. Most studies on MARCH8 have focused on RNA viruses, leaving its role in DNA viruses largely unexplored. Pseudorabies virus (PRV) is a large DNA virus that poses a potential threat to humans. In this study, we found that MARCH8 inhibited PRV replication at the cell-to-cell fusion stage. Interestingly, our findings proved that MARCH8 blocks gB cleavage by recruiting furin but this activity does not inhibit viral infection in vitro. Furthermore, we confirmed that MARCH8 inhibits cell-to-cell fusion independent of its E3 ubiquitin ligase activity but dependent on the interaction with the cell-to-cell fusion complex (gB, gD, gH, and gL). Finally, we discovered that the distribution of the cell-to-cell fusion complex is significantly altered and trapped within the trans-Golgi network. Overall, our results indicate that human MARCH8 acts as a potent antiviral host factor against PRV via trapping the cell-to-cell fusion complex in the trans-Golgi network.
摘要：
膜相关RING-CH8蛋白（MARCH8），E3泛素连接酶家族的成员，具有广谱抗病毒活性。然而,一些病毒劫持MARCH8来促进病毒复制，强调其在病毒生命周期中的双重作用。大多数关于MARCH8的研究都集中在RNA病毒上，其在DNA病毒中的作用尚未被研究。伪狂犬病病毒（PRV）是一种大型DNA病毒，对人类构成潜在威胁。在这项研究中,我们发现MARCH8在细胞与细胞融合阶段抑制PRV复制.有趣的是,我们的发现证明MARCH8通过招募弗林蛋白酶阻断gB裂解，但这种活性在体外不抑制病毒感染。此外，我们证实MARCH8抑制细胞-细胞融合，而不依赖于其E3泛素连接酶活性，但依赖于与细胞-细胞融合复合物的相互作用（gB，gD,gH,和gL）。最后,我们发现细胞与细胞融合复合物的分布发生了明显的变化，并被捕获在反式高尔基体网络中。总的来说,我们的结果表明，人类MARCH8通过捕获跨高尔基体网络中的细胞间融合复合物，作为抗PRV的有效抗病毒宿主因子。
