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

B Marchetti; G H Ashrafi; E S Dornan; E H Araibi; S A Ellis; M S Campo

doi:10.1038/sj.onc.1209245

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

Oncogene. 2006 Apr 6;25(15):2254-63. doi: 10.1038/sj.onc.1209245.

Authors

B Marchetti¹, G H Ashrafi, E S Dornan, E H Araibi, S A Ellis, M S Campo

Affiliation

¹ Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Glasgow, UK.

PMID: 16288210
DOI: 10.1038/sj.onc.1209245

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / pharmacology
Bovine papillomavirus 1 / pathogenicity
Bovine papillomavirus 4
Cattle
Cell Transformation, Viral
Cysteine Proteinase Inhibitors / pharmacology
Down-Regulation
Enzyme Inhibitors / pharmacology
Fetus
Golgi Apparatus / metabolism*
Histocompatibility Antigens Class I / metabolism*
Immunoprecipitation
Interferon-beta / pharmacology
Interferon-gamma / pharmacology
Leupeptins / pharmacology
Macrolides / pharmacology
Oncogene Proteins, Viral / genetics
Oncogene Proteins, Viral / metabolism*
Protein Biosynthesis
Protein-Tyrosine Kinases / metabolism
Sequence Deletion
Transcription, Genetic
Vacuolar Proton-Translocating ATPases / antagonists & inhibitors
Vacuolar Proton-Translocating ATPases / metabolism

Substances

Antiviral Agents
Cysteine Proteinase Inhibitors
Enzyme Inhibitors
Histocompatibility Antigens Class I
Leupeptins
Macrolides
Oncogene Proteins, Viral
bafilomycin A
Interferon-beta
Interferon-gamma
Protein-Tyrosine Kinases
Vacuolar Proton-Translocating ATPases
benzyloxycarbonylleucyl-leucyl-leucine aldehyde