The E5 protein of the human papillomavirus type 16 down-regulates HLA-I surface expression in calnexin-expressing but not in calnexin-deficient cells.
The human papillomavirus type 16 E5 protein (HPV16 E5) down-regulates surface expression of HLA-I molecules. The molecular mechanisms underlying this effect are so far unknown. Here we show that HPV16 E5 down-regulates HLA-I surface expression in calnexin-containing but not in calnexin-deficient cells. Immunoprecipitation experiments reveal that calnexin and HPV16E5 can be co-precipitated and that this association depends on the presence of a wild-type first hydrophobic region of E5. When an E5 mutant (M1) in which the first putative transmembrane helix had been disrupted was used for the transfections calnexin-E5 co-precipitation was strongly impaired. In addition, we show that the M1 mutant is only able to marginally down-regulate HLA-I surface expression compared to the wild-type protein. Besides, we demonstrate that E5 forms a ternary complex with calnexin and the heavy chain of HLA-I, which is mediated by the first hydrophobic region of the E5 protein. On the basis of our results we conclude that formation of this complex is responsible for retention of HLA-I molecules in the ER of the cells.
Gruener
Myriam
M
Division of Cell Differentiation, German Cancer Research Center, Heidelberg, Germany. m.gruener@dkfz.de
Bravo
Ignacio G
IG
Momburg
Frank
F
Alonso
Angel
A
Tomakidi
Pascal
P
D037281:Calnexin / Q000172:deficiency / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D015870:Gene Expression; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism / Q000502:physiology*; D000086082:Viroporin Proteins
D037281:Calnexin; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins