The E5 oncoprotein of BPV-4 does not interfere with the biosynthetic pathway of non-classical MHC class I.
The major histocompatibility complex (MHC) class I region in mammals contains both classical and non-classical MHC class I genes. Classical MHC class I molecules present antigenic peptides to cytotoxic T lymphocytes, whereas non-classical MHC class I molecules have a variety of functions. Both classical and non-classical MHC molecules interact with natural killer cell receptors and may under some circumstances prevent cell death by natural killer cytotoxicity. The E5 oncoprotein of BPV-4 down-regulates the expression of classical MHC class I on the cell surface and retains the complex in the Golgi apparatus. The inhibition of classical MHC class I to the cell surface results from both the impaired acidification of the Golgi, due to the interaction of E5 with subunit c of the H+ V-ATPase, and to the physical binding of E5 to the heavy chain of MHC class I. Despite the profound effect of E5 on classical MHC class I, E5 does not retain a non-classical MHC class I in the Golgi, does not inhibit its transport to the cell surface and does not bind its heavy chain. We conclude that, as is the case for HPV-16 E5, BPV-4 E5 does not down-regulate certain non-classical MHC class I, potentially providing a mechanism for the escape of the infected cell from attack by both cytotoxic T lymphocytes and NK cells.
Araibi
E H
EH
Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Garscube Estate, Glasgow G61 1QH, Scotland, UK.
Marchetti
B
B
Dornan
E S
ES
Ashrafi
G H
GH
Dobromylskyj
M
M
Ellis
S A
SA
Campo
M S
MS
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000145:classification / Q000502:physiology*; D052697:Bovine papillomavirus 4; D002417:Cattle; D045744:Cell Line, Tumor; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D034801:Mastocytoma / Q000473:pathology; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral