The E5 oncoprotein of BPV-4 does not interfere with the biosynthetic pathway of non-classical MHC class I

• Published in: Virology (New York, N.Y.) N.Y.), 2006-09, Vol.353 (1), p.174-183
• Main Authors: Araibi, E.H., Marchetti, B., Dornan, E.S., Ashrafi, G.H., Dobromylskyj, M., Ellis, S.A., Campo, M.S.
• Format: Article
• Language: English
• Subjects: Animals; Bovine papillomavirus 1 - classification; Bovine papillomavirus 1 - physiology; Bovine papillomavirus 4; BPV; Cattle; Cell Line, Tumor; Classical MHC class I; E5-MHC class I interaction; Histocompatibility Antigens Class I - metabolism; Mastocytoma - pathology; MHC class I down-regulation; Mice; Non-classical MHC class I; Oncogene Proteins, Viral - physiology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.05.031

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.