Study of papillomavirus latent infection in an animal model.
Doctoral thesis, UCL (University College London).
Papillomaviruses cause a wide spectrum of benign and neoplastic diseases in humans and animals. They may also cause infections that are characterised by the absence of clinical signs of disease and some of these may represent viral latency. Many viruses have a latent stage of their life cycle and papillomaviruses appear to be no different. For example, some low-risk human papillomavirus types such as HPV-11 and HPV-6 can cause infections that resemble latency. It has recently been shown that rabbit oral papillomavirus (ROPV) is an appropriate model of these virus types. Infection of the tongue mucosa with ROPV leads to the formation of benign papillomas that form and regress within a matter of weeks. In this thesis, we show that ROPV is a suitable model system for the study of latent papillomavirus infections. The regression of ROPV papillomas is followed by the persistence of viral DNA and RNA in the absence of clinical signs of disease. Persistence of ROPV DNA is generally restricted to basal epithelial cells at sites of previous infection. Low copy numbers of viral DNA in the basal layer are compatible with infection remaining in only a subset of these cells (possibly epithelial stem cells). Typically there is no amplification of viral DNA in the upper layers of the epithelium. ROPV proteins are undetectable during latency suggesting that the productive stages of the life cycle are not completed. Low levels of ROPV early transcripts are detectable and it is possible that early proteins are necessary to allow stable maintenance of viral episomes in basal epithelial cells. We attempt to demonstrate the ability of latent ROPV infection to reactivate to form clinical disease. Evidence of spontaneous reactivation was seen on one occasion, but efforts to initiate reactivation by immunosuppressing rabbits were hampered by the toxicity of the drugs used. However, our preliminary data suggest that immunosuppression of rabbits can cause reactivation of latent ROPV.
|Title:||Study of papillomavirus latent infection in an animal model|
|Additional information:||Permission for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Infection and Immunity (Division of)|
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