The E5 protein of BPV-4 interacts with the heavy chain of MHC class I and irreversibly retains the MHC complex in the Golgi apparatus.
BPV-4 E5 inhibits transcription of the bovine MHC class I heavy chain (HC) gene, increases degradation of HC and downregulates surface expression of MHC class I by retaining the complex in the Golgi apparatus (GA). Here we report that transcription inhibition can be alleviated by interferon treatment and the degradation of HC can be reversed by treatment with inhibitors of proteasomes and lysosomes. However, the inhibition of transport of MHC class I to the cell surface is irreversible. We show that E5 is capable of physically interacting with HC. Together with the inhibition of the vacuolar ATPase (due to the interaction between E5 and 16k subunit c), the interaction between E5 and HC is likely to be responsible for retention of MHC class I in the GA. C-terminus deletion mutants of E5 are incapable of either downregulating surface MHC class I or interacting with HC, establishing that the C-terminus domain of E5 is important in the inhibition of MHC class I.
Marchetti
B
B
Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Glasgow, UK.
Ashrafi
G H
GH
Dornan
E S
ES
Araibi
E H
EH
Ellis
S A
SA
Campo
M S
MS
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D052688:Bovine papillomavirus 1 / Q000472:pathogenicity; D052697:Bovine papillomavirus 4; D002417:Cattle; D002472:Cell Transformation, Viral; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus; D006056:Golgi Apparatus / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D047468:Immunoprecipitation; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017384:Sequence Deletion; D014158:Transcription, Genetic; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000998:Antiviral Agents; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D015395:Histocompatibility Antigens Class I; D007976:Leupeptins; D018942:Macrolides; D009856:Oncogene Proteins, Viral; C057620:bafilomycin A; D016899:Interferon-beta; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D025262:Vacuolar Proton-Translocating ATPases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde