The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review

Graham, S. V. (2017) The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review. Clinical Science, 131(17), pp. 2201-2221. (doi: 10.1042/CS20160786) (PMID:28798073)

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Abstract

HPVs (human papillomaviruses) infect epithelial cells and their replication cycle is intimately linked to epithelial differentiation. There are over 200 different HPV genotypes identified to date and each displays a strict tissue specificity for infection. HPV infection can result in a range of benign lesions, for example verrucas on the feet, common warts on the hands, or genital warts. HPV infects dividing basal epithelial cells where its dsDNA episomal genome enters the nuclei. Upon basal cell division, an infected daughter cell begins the process of keratinocyte differentiation that triggers a tightly orchestrated pattern of viral gene expression to accomplish a productive infection. A subset of mucosal-infective HPVs, the so-called ‘high risk’ (HR) HPVs, cause cervical disease, categorized as low or high grade. Most individuals will experience transient HR-HPV infection during their lifetime but these infections will not progress to clinically significant cervical disease or cancer because the immune system eventually recognizes and clears the virus. Cancer progression is due to persistent infection with an HR-HPV. HR-HPV infection is the cause of >99.7% cervical cancers in women, and a subset of oropharyngeal cancers, predominantly in men. HPV16 (HR-HPV genotype 16) is the most prevalent worldwide and the major cause of HPV-associated cancers. At the molecular level, cancer progression is due to increased expression of the viral oncoproteins E6 and E7, which activate the cell cycle, inhibit apoptosis, and allow accumulation of DNA damage. This review aims to describe the productive life cycle of HPV and discuss the roles of the viral proteins in HPV replication. Routes to viral persistence and cancer progression are also discussed.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Professor Sheila
Authors: Graham, S. V.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Clinical Science
Publisher:Portland Press
ISSN:0143-5221
ISSN (Online):1470-8736
Published Online:10 August 2017

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
507841Human papillomavirus E2 regulation of splicing factors: consequences for the virus life cycleSheila GrahamWellcome Trust (WELLCOTR)088848/Z/09/ZMVLS III - CENTRE FOR VIRUS RESEARCH