The luminal part of the murine cytomegalovirus glycoprotein gp40 catalyzes the retention of MHC class I molecules

Abstract

Murine cytomegalovirus (MCMV) interferes with the MHC class I pathway of antigen presentation. The type I transmembrane glycoprotein gp40, encoded by the gene m152 , retains major histocompatibility complex (MHC) class I complexes in the endoplasmic reticulum (ER)–Golgi intermediate compartment (ERGIC)/ cis ‐Golgi. These MHC class I complexes are stable, show an extended half‐life and do not exchange β2‐microglobulin, whereas gp40 reaches an endosomal/lysosomal compartment where it subsequently is degraded. The analysis of regions within the viral protein that are essential for MHC class I retention revealed that a secreted form of gp40, lacking the cytoplasmic tail and the transmembrane region, still has the capacity to retain MHC class I complexes. Continuous expression of gp40 is not required for MHC class I retention. Our data indicate that the retention of MHC class I complexes in the ERGIC/ cis ‐Golgi is triggered by gp40 and does not require the further presence of the viral protein.