Pseudorabies virus US3- and UL49.5-dependent and -independent downregulation of MHC I cell surface expression in different cell types

Many herpesviruses interfere with the MHC I antigen-processing pathway in order to limit elimination by cytotoxic T-lymphocytes. For varicelloviruses, the largest subgroup of alphaherpesviruses, two viral proteins have been reported to downregulate MHC I cell surface expression: UL49.5 for BoHV-1, PRV, and EHV-1 and the US3 orthologue for VZV. Here, we report that PRV reduces MHC I cell surface expression during infection in a cell-type-dependent manner. In ST cells, a kinase-active US3 was necessary but not sufficient to downregulate cell surface MHC I expression, whereas US3 was not required in PK-15 cells and porcine alveolar macrophages (PAM). MHC I downregulation was not (PAM, ST) or only partly (PK-15) dependent on UL49.5. In conclusion, we show that the mechanism(s) of PRV-mediated cell surface MHC I downregulation are cell-type-dependent, with variable roles for US3, UL49.5, and additional, yet unidentified early viral proteins.