Abstract：
The membrane-associated RING-CH (MARCH) family of proteins are members of the E3 ubiquitin ligase family and are essential for a variety of biological functions. Currently, MARCH proteins are discovered to execute antiviral functions by directly triggering viral protein degradation or blocking the furin cleavage of viral class I fusion proteins. Here, we report a novel antiviral mechanism of MARCH1 and MARCH2 (MARCH1/2) in the replication of Pseudorabies virus (PRV), a member of the Herpesviridae family. We discovered MARCH1/2 restrict PRV replication at the cell-to-cell fusion step. Furthermore, MARCH1/2 block gB cleavage, and this is dependent on their E3 ligase activity. Interestingly, the blocking of gB cleavage by MARCH1/2 does not contribute to their antiviral activity in vitro. We discovered that MARCH1/2 are associated with the cell-to-cell fusion complex of gB, gD, gH, and gL and trap these viral proteins in the trans-Golgi network (TGN) rather than degrading them. Overall, we conclude that MARCH1/2 inhibit PRV by trapping the viral cell-to-cell fusion complex in TGN.
摘要：
膜相关的RING-CH(MARCH)蛋白家族是E3泛素连接酶家族的成员,并且对于多种生物学功能是必需的。目前,发现MARCH蛋白通过直接触发病毒蛋白降解或阻断病毒I类融合蛋白的弗林蛋白酶裂解来执行抗病毒功能。这里,我们报道了MARCH1和MARCH2（MARCH1/2）在伪狂犬病病毒（PRV）复制中的一种新的抗病毒机制，疱疹病毒科的成员。我们发现MARCH1/2在细胞与细胞融合步骤限制PRV复制。此外，MARCH1/2阻断gB裂解，这取决于它们的E3连接酶活性。有趣的是,通过MARCH1/2阻断gB切割不有助于其体外抗病毒活性。我们发现MARCH1/2与gB的细胞-细胞融合复合物有关，gD,gH,和gL，并将这些病毒蛋白捕获在反式高尔基网络（TGN）中，而不是降解它们。总的来说,我们得出的结论是,MARCH1/2通过在TGN中捕获病毒细胞间融合复合物来抑制PRV.
