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

作者：Schempp Susanne; Topp Max; Kessler Tobias; Sampaio Kerstin Laib; Dennehy Kevin M; Einsele Hermann; Hahn Gabriele; Grigoleit Goetz Ulrich; Jahn Gerhard^*

来源：Virus Research, 2011, 155(2): 446-454.

DOI：10.1016/j.virusres.2010.11.014

• Human cytomegalovirus
• Dendritic cells
• Stem cell transplantation
• Adaptive immune response

A HCMV mutant of endothelial- and DC-tropic strain TB40/E lacking the described MHC downregulating genes US2-6 and US11 (RVTB40/E(4)Delta US11) was generated. We analyzed the susceptibility of DC to RVTB40/E(4)Delta US11 and subsequently studied antigen presentation and 1-cell stimulation. Wildtype TB40/E- and RVTB40/E(4)Delta US11 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)Delta US11-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-gamma 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-gamma production, RVTB40/E(4)Delta US11-infected DC efficiently stimulated CD8+ T-cells to produce IFN-gamma.

• 出版日期2011-2
• 单位河北医科大学