Cellular pathology critical review assignment - Essay Example

The article explores the role of the Human Papillomavirus (HPV) - E5 oncoprotein. While it has been shown that bovine E5 protein impairs the synthesis, stability and transport of the major histocompatibility (MHC) type I complex, this study shows that the E5 protein expressed by HPV-16 and the low-risk virus HPV-6 causes a similar retention of the MHC molecules. The novel mechanism identified here is that the HPV-16 E5 protein only prevents the transport of the MHC molecules to the cell surface by selectively down regulating the expression of HLA molecules A and B, which present viral peptides to the cytotoxic T-lymphocytes, thereby avoiding their clearance from the body which leads to establishment of infection and later malignancy.

For the in vitro study immortalized human keratinocyte cell line HaCaT, primary bovine PalF cells and NIH 3T3 cell lines which expressed the HPV-16 E5 protein was used and some NIH 3T3 expressed HPV-6 E5. After subsequent culture, suitable immunological assays were carried out to detect the presence and localization of the MHC class I molecules in these cells. While in the control cell lines MHC molecules were localized both in the cell surface and within the GA, in the HPV-16 E5 expressing cells the molecules were found exclusively in the GA.

The study also showed that HPV-16 E5 did not affect the synthesis of MHC molecules unlike BPV E5 and that the expression of the E5 protein did no affect the transporter protein responsible for the transport of MHC molecules. To determine the effect of interferon, all the cell lines were treated with interferon β, which resulted in all the cell lines having similar levels of MHC molecules and also the molecules were found on the cell surface in the E5 expressing cell lines thus proving that the inhibition on transport of MHC molecules is reversed upon treatment with interferon.

The study also noted that E5 did not down regulate the expression of HLA-C and E, involved in inhibiting NK cell-mediated lysis. The two most striking limitations observed is: the study was carried out in vitro and in vivo reproducibility needs to be ascertained and secondly, the detection of the E5 protein was carried out by RT-PCR rather simpler techniques. The two major strengths include: this is the first paper to show the immune evasion mechanism by the HPV E5 protein and the cell lines used are a good model for understanding the mechanism and finally, the study explores the gene level expressions involved in the down regulation process of the MHC molecules.

In conclusion, the methods used, results obtained and the discussion have been sufficiently justified and they are in support of the hypothesis that the E5 protein of HPV, like that of BPV, plays a major role in the immune evasion mechanisms. ReferenceAshrafi, G.H., Haghshenas, M.R., Marchetti, B., O’Brien, P.M. & Campo, M.S. 2005. E5 Protein of Human Papillomavirus Type 16 Selectively Downregualtes Surface HLA Class I. International Journal of Cancer, 113: 276-283.