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

• Published in: The EMBO journal 2000-03, Vol.19 (5), p.870-881
• Main Authors: Ziegler, Heike, Muranyi, Walter, Burgert, Hans-Gerhard, Kremmer, Elisabeth, Koszinowski, Ulrich H.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; AIDS/HIV; Animals; Antigen Presentation; cis-Golgi retention; Cytomegalovirus; ERGIC; glycoprotein gp40; Herpesviridae Infections - immunology; immune evasion; m152 gene; Major Histocompatibility Complex - immunology; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; MHC class I pathway; Mice; murine cytomegalovirus; Muromegalovirus - immunology; Mutation; Retention; Retroviridae Proteins - chemistry; Retroviridae Proteins - genetics; Retroviridae Proteins - immunology
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1093/emboj/19.5.870

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 β 2 ‐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.