E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domai

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Ashrafi, G.H. ; Haghshenas, M. ; Marchetti, B. ; Campo, M.S. (2006)

Human papillomavirus type 16 E5 protein (HPV-16 E5) is expressed early in papillomavirus infection and is localised primarily in the cell Golgi apparatus (GA) and endoplasmic reticulum. E5 prevents transport of the major histocompatibility class I (MHC I; HLA class I in humans) to the cell surface and retains the complex in the GA. We report that these effects are due, at least in part, to the interaction between E5 and HLA I heavy chain (HC). We also demonstrate that the down-regulation of surface HLA I and interaction with HC are mediated by the first hydrophobic domain of E5. Although E5 downregulates classical HLA selectively as it does not downregulate non-classical HLA, the interaction with the HC of classical HLA I is not specific for a particular haplotype of HLA I. This suggests that E5 can interfere with antigen presentation by most, if not all, classical HLA I haplotypes, with potentially serious consequences as the ability of infected cells to present antigenic peptides to effector T cells would be compromised.
  • References (31)
    31 references, page 1 of 4

    1. Frazer IH, Thomas R, Zhou J, Leggatt G, Dunn L, McMillan N, Tindle RW, Filgueira L, Manders P, Barnard P, Sharkey M. Potential strategies utilised by papillomavirus to evade host immunity. Immunol. Rev. 1999;168:131-42.

    2. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nature Reviews, Cancer 2002;2:342-50.

    3. Cresswell P, Bangia N, Dick T, Dietrich G. The nature of the MHC class I peptide loading complex. Immunological Reviews 1999;172:21-28.

    4. Ashrafi GH, Haghshenas MR, Marchetti B, O'Brien PM, Campo MS. The E5 protein of human papillomavirus type 16 selectively down-regulates surface HLA class. International Journal of Cancer 2005;113:276-83.

    5. Chang JL, Tsao YP, Liu DW, Huang SJ, Lee WH, Chen SL. The expression of HPV-16 E5 protein in squamous neoplastic changes in the uterine cervix. J Biomed Sci 2001;8:206-13.

    6. Kell B, Jewers RJ, Cason J, Pakarian F, Kaye JN, Best JM. Detection of E5 oncoprotein in human papillomavirus type 16-positive cervical scrapes using antibodies raised to synthetic peptides. J Gen Virol 1994;75:2451-6.

    7. Suprynowicz FA, Campo, M.S., Schlegel, R. Biological Activities of Papillomavirus E5 Proteins. In: Campo MS. Papillomavirus Research: From Natural History To Vaccines and Beyond. Caister Academic Press, 2006:97-113.

    8. Rodriguez MI, Finbow ME, Alonso A. Binding of human papillomavirus 16 E5 to the 16 kDa subunit c (proteolipid) of the vacuolar H+-ATPase can be dissociated from the E5- mediated epidermal growth factor receptor overactivation. Oncogene 2000;19:3727-32.

    9. Ashrafi GH, Tsirimonaki E, Marchetti B, O'Brien PM, Sibbet GJ, Andrew L, Campo MS. Down-regulation of MHC class I by bovine papillomavirus E5 oncoproteins. Oncogene 2002;21:248-59.

    10. Marchetti B, Ashrafi GH, Araibi EH, Ellis SA, Campo MS. 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;27:2254-2263

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