Transformed cells expressing BPV-1 E5 or BPV-4 E5 retain major histocompatibility class I (MHC I) molecules in the Golgi apparatus and cause the inhibition of transport of the complex to the cell surface. This effect can be ascribed to a failure of acidification of the Golgi apparatus. In addition, the total amount of both MHC I protein and mRNA is reduced in E5-transformed cells. Results from this thesis show that: a) Transcription inhibition can be alleviated by interferon treatment and the degradation of MHC I heavy chain (HC) can be reversed by treatment with inhibitors of proteasomes and lysosomes. However, the inhibition of transport of MHC I to the cell surface is irreversible. b) E5 is capable of physically interacting with heavy chain. Together with the inhibition of the vacuolar (ATPase (due to the interaction between E5 and 16k subunit c), the interaction between E5 and heavy chain is likely to be responsible for retention of MHC I in the Golgi apparatus. c) C-terminus deletion mutants of E5 are incapable of either down-regulating surface MHC class I or interacting with heavy chain, establishing that the C-terminus domain of E5 is important in the inhibition of MHC I. d) Other two PV E5 proteins, BPV-1 E5 and HPV-16 E5 are able to interact physically with heavy chains from different alleles. BPV-1 E5 interacts with two equine classical class I heavy chains (EqB2 and EqB4) in vitro and the HPV-16 E5 interacts with classical HLA-A1, A2 and B8 in vitro and with HLA-A3 in vivo. e) Like HPV-16 E5, BPV-4 E5 is incapable of down-regulating certain non-classical MHC genes. These observations lead to a deeper understanding of the general down-regulation of MHC class I by the E5 proteins. Lack of surface classical MHC class I and presence of non-classical MHC class I in infected cells expressing E5 would allow evasion of cytotoxic T lymphocyte and NK killing and thus establishment of viral infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:486933 |
| Date | January 2006 |
| Creators | Marchetti, Barbara |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/5582/ |
Page generated in 0.0017 seconds