Mpox virus OPG175 negatively regulates viral replication via controlling Wnt signaling

Mpox virus (MPXV) infection has different case fatality rates and symptoms depending on its clade. However, there has not been sufficient molecular biological analysis of the differences between clades. Here, we investigated whether we can distinguish between clades by focusing on the expression of MPXV genes. The replication efficiency of MPXV clade IIb, responsible for the 2022 Mpox outbreak, was lower than that of clades Ia and IIa. We found that OPG175 was highly expressed in MPXV clade IIb-infected cells. Suppression of OPG175 expression significantly upregulated the infectious titer of MPXV, while OPG175 overexpression significantly decreased the infectious titer of MPXV. We found OPG175 overexpression to enhance the expression of Wnt signaling-related genes and activation of Wnt signaling to decrease the replication efficiency of MPXV. Therefore, high OPG175 expression in MPXV clade IIb-infected cells likely inhibits MPXV replication via activation of Wnt signaling.