Deletion mutant of human cytomegalovirus lacking US2-US6 and US11 maintains MHC class I expression and antigen presentation by infected dendritic cells.

A HCMV mutant of endothelial- and DC-tropic strain TB40/E lacking the described MHC downregulating genes US2-6 and US11 (RVTB40/E(4)ΔUS11) was generated. We analyzed the susceptibility of DC to RVTB40/E(4)ΔUS11 and subsequently studied antigen presentation and T-cell stimulation. Wildtype TB40/E- and RVTB40/E(4)ΔUS11 showed no significant difference in the efficiency of infection of DC. Whereas infection with TB40/E induced downregulation of MHC I, no significant MHC I downregulation was observed on RVTB40/E(4)ΔUS11-infected DC, indicating that the US2-6, US11 region encodes for the major genes relevant for MHC I downregulation. However, both viruses induced downregulation of MHC II, as well as CD40, CD80, CD86 and CD83 to the same levels. Stimulation of IFN-γ production by HCMV-specific CD8+ T-cells by infected autologous DC correlated with the modulation of MHC expression. While TB40/E-infected DC did not efficiently stimulate IFN-γ production, RVTB40/E(4)ΔUS11-infected DC efficiently stimulated CD8+ T-cells to produce IFN-γ.