Human papillomaviruses (HPV) infect and replicate in stratified epithelial cells of the skin and mucosal surfaces where they can cause benign lesions, or pre-malignant and malignant disease. The papillomaviruses can therefore by divided into low and high risk types depending on their pathology. A common feature of both groups is their ability to persist in the host without stimulating any effective immune response, so that lesions persist for months or even years. Regression does, however, occur spontaneously and is immunogically mediated.. The natural history of infection suggests that the virus has evolved mechanisms to impair an effective immune response from being generated by the host. The host cell of the virus is the keratinocyte, have evidence that the E6 proteins of HPV type 16 inhibits the production of cytokines produced by keratinocytes and so may inhibit stimulation of an effective immune response. In this project we wish to expand these initial observations to determine if other HPV types modulate stimulatory or inhibitory cytokines and to investigate if keratinocytes expressing HPV genes change the functional properties of skin dendritic cells, so that they can no longer stimulate an effective immune response.
| Divekar, Anagha A; Zaiss, Dietmar M W; Lee, F Eun-Hyung et al. (2006) Protein vaccines induce uncommitted IL-2-secreting human and mouse CD4 T cells, whereas infections induce more IFN-gamma-secreting cells. J Immunol 176:1465-73 |
| Guess, Jennifer C; McCance, Dennis J (2005) Decreased migration of Langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced macrophage inflammatory protein-3alpha production. J Virol 79:14852-62 |
