Abstract
Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.
Highlights
Papillomaviruses have been discovered in a wide array of vertebrates.More than 300 papillomaviruses have been identified and completely sequenced, including over 200 human papillomaviruses (PaVE: Papillomavirus Episteme [1])
Changes in the epithelial micro-environment, as can occur following immunosuppression or in individuals suffering from epidermodysplasia verruciformis (EV), can allow these human papillomavirus (HPV) types to produce visible papillomas, and in some situations can facilitate the development of cancers [10]
The association between HPV16 and cervical cancer is more than 10 times stronger than that between either HPV31 or HPV35 [37], and of these three types, HPV16 is uniquely associated with tumours of the oropharyngeal region [38]
Summary
Papillomaviruses have been discovered in a wide array of vertebrates. More than 300 papillomaviruses have been identified and completely sequenced, including over 200 human papillomaviruses (PaVE: Papillomavirus Episteme [1]). Certain Beta HPV types are a significant cause of non-Melanoma skin cancer in susceptible individuals, the molecular mechanism by which they facilitate cancer progression appears to be somewhat different from what has been worked out for the Alphapapillomavirus types [11] When considered together, it appears that different papillomavirus types have evolved distinct life-cycle strategies, which allow them to thrive and produce viral progeny at different epithelial sites. The association between HPV16 and cervical cancer is more than 10 times stronger than that between either HPV31 or HPV35 [37], and of these three types, HPV16 is uniquely associated with tumours of the oropharyngeal region [38] To explain this will require a dissection of virus-specific gene expression at this particular epithelial site, and an understanding of virus protein function and the extent to which proteins encoded by different HPV types affect common molecular pathways. To cancer progression following infection by certain β HPV types as well as for the high-risk
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