Identification of a genomic region within MCMV critical for the export of m4/Kb complexes (105.17)

Abstract

Abstract The murine cytomegalovirus (MCMV) protein m4/gp34 binds to major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum (ER), and this stable m4/gp34-MHC class I complex is then exported to the cell surface. m4/gp34 can impact antigen presentation to CD8 T cells either positively or negatively. However, its main role may be to interact with natural killer (NK) cells. Recent evidence indicates that m4/gp34 in combination with the MHC class I molecule H-2Dk stimulates the activating NK receptor Ly49P. m4/gp34 is retained in the ER unless it binds to MHC class I. The goal of this study was to understand the molecular basis for export of the m4/gp34-MHC class I complex. We found that when m4/gp34 was expressed in a gutless adenovirus vector, it readily formed complexes with MHC class I. However, the complexes were retained in the ER. Superinfection with MCMV lacking m4 restored the export of m4/gp34-Kb complexes. Screening a panel of virus mutants revealed that a region of the MCMV genome containing open reading frames (ORFs) m166-m170 was needed for efficient export of m4/gp-34-Kb complexes. We will present data describing the impact of individual ORFs within this region on the export of m4/gp34-Kb complexes and on the biological function of m4/gp34.