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Doorbar group:

Human Papillomavirus

Human papillomaviruses cause epithelial lesions of varying severity. Over 100 different human papillomavirus (HPV) types have been identified and each is associated with a different type of lesion. HPV type 1 causes verrucas, HPV type 2 causes common warts and HPV type 11 causes genital warts (Doorbar and Sterling, 2001). Certain HPV types, such as HPV16 and HPV18 infect cervical epithelium and cause lesions that can progress through different grades of cervical intraepithelial neoplasia to cancer. These viruses are known as ‘high-risk’ papillomaviruses. Most ‘high-risk’ HPV infections are successfully resolved by the host immune system and do not become life-threatening. In a small number of cases however, lesions caused by ‘high-risk’ HPV types can persist and can develop into cancer.

Female cancer incidence worldwide ::

Pie chart showing incidence of female cancer worldwide
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Cervical cancer is the second most common female cancer worldwide with around half a million cases each year (WHO/IARC statistics)

Over 99.7% of all cervical cancers contain HPV DNA. It is now widely accepted that human papillomaviruses are the cause of nearly all cervical cancers.

Our work is divided into three areas:

  1. The first aims to understand how the papillomavirus life cycle is organised and aims to identify the changes that occur during cervical cancer progression. This has lead to the identification of biomarkers for cervical cancer screening.
  2. The second part of our work uses mutant viral genomes to establish the importance of particular viral gene products for life cycle completion. We are currently focusing on the viral proteins required for amplification of the viral genome in preparation for virus assembly.
  3. The third part of our work aims to establish the function of these viral proteins at the molecular level. So far we have concentrated on the HPV E4 protein. E4 is expressed at the time of viral genome amplification and can arrest cells in the G2 phase of the cell cycle.

Selected publications ::

  • Davy CE, Jackson DJ, Wang Q, Raj K, Masterson PJ, Fenner NF, Southern S, Cuthill S, Millar JB, and Doorbar, J. (2002).
    Identification of a G(2) arrest domain in the E1^E4 protein of human papillomavirus type 16.
    J Virol     76(19), 9806-9818.
  • Peh WL, Middleton K, Christensen N, Nicholls P, Egawa K, Sotlar K, Brandsma J, Percival A, Lewis J, Liu WJ, and Doorbar, J. (2002).
    Life cycle heterogeneity in animal models of human papillomavirus-associated disease.
    J Virol     76(20), 10401-10416.
  • Doorbar, J., and Sterling, J. C. (2001).
    The biology of human papillomaviruses.
    In     "Human Papillomaviruses" (J. C. Sterling, and S. K. Tyring, Eds.), pp. 10-23. Arnold, London.
  • Doorbar, J., Elston, R., Napthine, S., Raj, K., Medcalf, E., Jackson, D., Coleman, N., Griffin, H., Masterson, P., Stacey, S., Mengitsu, Y., and Dunlop, J. (2000).
    The E1^E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus.
    J. Virol     74(21), 10081-10095.
  • Doorbar, J., Foo, C., Coleman, N., Medcalf, E., Hartley, O., Prospero, T., Napthine, S., Sterling, J., Winter, G., and Griffin, H. (1997).
    Characterisation of events during the late stages of HPV16 infection in vivo using high affinity synthetic Fabs to E4.
    Virology     238, 40-52.
  • Doorbar, J., and Myers, G. (1996).
    The E4 protein.
    In     "Human Papillomaviruses 1996" (G. Myers, H. Delius, J. Icenogel, H.-U. Bernard, C. Baker, A. Halpern, and C. Wheeler, Eds.), Vol. III, pp. 58-80. Los Alamos National Laboratory, Los Alamos, New Mexico, USA.