Rapid degradation of the heavy chain of class I major histocompatibility complex antigens in the endoplasmic reticulum of human cytomegalovirus-infected cells.
Human cytomegalovirus (HCMV) infection results in a marked reduction in the surface expression of class I major histocompatibility complex antigens on the host cells, which is thought to be one of the means for HCMV to evade the host immune system. To clarify the precise mechanism(s) of this phenomenon, we investigated the fate of the heavy chain of class I major histocompatibility complex antigens in HCMV-infected human embryonic lung fibroblasts (HEL) by pulse-chase analysis and immunocytochemical techniques. In HCMV-infected HEL, the heavy chain was synthesized at an increasing rate. However, instead of being transported to the cell surface through the Golgi apparatus, it was retained in the endoplasmic reticulum (ER) without acquisition of a complex-type N-linked oligosaccharide. In addition, it was rapidly degraded, with a half time of 20 min, and the amount of the heavy chain remaining at the end of 3 h of chase was 10% (or less) of that initially synthesized. ER degradation of host glycoproteins in HCMV-infected HEL was selective for the heavy chain, since the posttranslational processing of the transferrin receptor in these cells was not affected. The heavy chain degradation in infected cells was resistant to inhibitors of a lysosomal proteolytic pathway and to metabolic poisons. These observations suggest the presence of an energy-dependent nonlysosomal proteolytic pathway in the ER.
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Y
Y
Yamashita
K
K
Shimokata
S
S
Saga
S
S
Mizuno
T
T
Tsurumi
Y
Y
Nishiyama
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D004622:Embryo, Mammalian; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000821:virology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D006056:Golgi Apparatus / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008168:Lung; D046911:Macromolecular Substances; D009844:Oligosaccharides / Q000302:isolation & purification / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013696:Temperature
D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D009844:Oligosaccharides; D017485:1-Deoxynojirimycin; D006026:Glycoside Hydrolases; C033424:N-methyldeoxynojirimycin