A mouse cytomegalovirus glycoprotein, gp34, forms a complex with folded class I MHC molecules in the ER which is not retained but is transported to the cell surface.
Murine cytomegalovirus (MCMV) interferes with antigen presentation by means of retaining major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum (ER). Here we identify and characterize an MCMV-encoded glycoprotein, gp34, which tightly associates with properly conformed MHC class I molecules in the ER. Gp34 is synthesized in large quantities during MCMV infection and it leaves the ER only in association with MHC class I complexes. Many but not all class I molecules are retained in the ER during the early phase of MCMV infection, and we observe an inverse correlation between amounts of gp34 synthesized during the course of infection and class I retention. An MCMV deletion mutant lacking several genes, including the gene encoding gp34, shows increased class I retention. Thus, MCMV gp34 may counteract class I retention, perhaps to decrease susceptibility of infected cells to recognition by natural killer cells.
Kleijnen
M F
MF
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Huppa
J B
JB
Lucin
P
P
Mukherjee
S
S
Farrell
H
H
Campbell
A E
AE
Koszinowski
U H
UH
Hill
A B
AB
Ploegh
H L
HL
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral; D020126:Brefeldin A; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology*; D005347:Fibroblasts / Q000821:virology; D005814:Genes, Viral / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006596:Hexosaminidases; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D017510:Protein Folding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017384:Sequence Deletion; D014764:Viral Proteins
D000914:Antibodies, Viral; D002352:Carrier Proteins; D003517:Cyclopentanes; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D011500:Protein Synthesis Inhibitors; D014764:Viral Proteins; C104832:gp34 protein, cytomegalovirus; D020126:Brefeldin A; D006596:Hexosaminidases