{Reference Type}: Journal Article
{Title}: MARCH1 and MARCH2 inhibit pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in trans-Golgi network.
{Author}: Huang R;Rao CH;Bai YZ;Yu C;Chen M;Peng JM;Xu SJ;Sun Y;Fandan M;Lyu C;Khan M;An TQ;Tian ZJ;Cai XH;Wang G;Tang YD;
{Journal}: Vet Microbiol
{Volume}: 295
{Issue}: 0
{Year}: 2024 Aug 22
{Factor}: 3.246
{DOI}: 10.1016/j.vetmic.2024.110164
{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.