E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domain.
Human papillomavirus type 16 E5 protein (HPV-16 E5) is expressed early in papillomavirus infection and is localised primarily in the cell Golgi apparatus (GA) and endoplasmic reticulum. E5 prevents transport of the major histocompatibility class I (MHC I; HLA class I in humans) to the cell surface and retains the complex in the GA. We report that these effects are due, at least in part, to the interaction between E5 and HLA I heavy chain (HC). We also demonstrate that the down-regulation of surface HLA I and interaction with HC are mediated by the first hydrophobic domain of E5. Although E5 downregulates classical HLA selectively as it does not downregulate non-classical HLA, the interaction with the HC of classical HLA I is not specific for a particular haplotype of HLA I. This suggests that E5 can interfere with antigen presentation by most, if not all, classical HLA I haplotypes, with potentially serious consequences as the ability of infected cells to present antigenic peptides to effector T cells would be compromised.
Ashrafi
G Hossein
GH
Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Glasgow, Scotland, UK.
Haghshenas
Mohammad
M
Marchetti
Barbara
B
Campo
M Saveria
MS
D002460:Cell Line; D017931:DNA Primers; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D016296:Mutagenesis; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000086082:Viroporin Proteins
D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins