Model systems of human papillomavirus‐associated disease

Abstract

Human papillomaviruses (HPVs) cause a range of serious diseases, including the vast majority of cervical cancers, most anal cancers and around half of head and neck cancers. They are also responsible for troublesome benign epithelial lesions, including genital warts and laryngeal papillomas, and in some individuals HPVs lead to recurrent respiratory papillomatosis and other difficult-to-manage diseases. As a result, there is a great need for model systems that accurately mimic papillomavirus infections in humans. This is complicated by the diverse variety of HPVs, which now number over 200 types, and the different strategies they have evolved to persist in the population. The most well-developed models involve the culture of HPV-containing keratinocytes in organotypic raft culture, an approach which appears to accurately mimic the life cycle of several of the high-risk cancer-associated HPV types. Included amongst these are HPV16 and 18, which cause the majority of cervical cancers. The low-risk HPV types persist less well in tissue-culture models, and our ability to study the productive life cycle of these viruses is more limited. Although ongoing research is likely to improve this situation, animal models of papillomavirus disease can provide considerable basic information as to how lesions form, regress and can be controlled by the immune system. The best studied are cottontail rabbit papillomavirus, rabbit oral papillomavirus and, more recently, mouse papillomavirus (MmuPV), the last of which is providing exciting new insights into viral tropisms and immune control. In addition, transgenic models of disease have helped us to understand the consequences of persistent viral gene expression and the importance of co-factors such as hormones and UV irradiation in the development of neoplasia and cancer. It is hoped that such disease models will eventually lead us to better understanding and better treatments for human disease.

MmuPV1 infection and tumor development of T cell-deficient mice is prevented by passively transferred hyperimmune sera from normal congenic mice immunized with MmuPV1 virus-like particles (VLPs)

“…These include bovine PV (BPV1 and BPV2), cotton rabbit PV (CRPV), and canine PV (COPV and CfPV2), all of which have been used for vaccine and pathogenesis studies (Campo, 2002;Buitrago-Pérez et al, 2012). In the absence of a proper mouse HPV model, transgenic mice were used for carcinogenesis and therapeutic vaccine studies (Doorbar, 2015;Eckert et al, 2000). Until recently, the only other PV associated with a mouse species was MmiPV1, which was isolated from a zoo colony of European harvest mice (Micromys minutus) (van Doorslaer et al, 2007;Sundberg et al, 1988).…”

Transcriptome analysis of Mastomys natalensis papillomavirus in productive lesions after natural infection

“…Although valuable research on HPV biology has emerged from in vitro systems or even human samples, a comprehensive understanding of disease progression has been hampered by the lack of appropriate animal models of HPV infection, since papillomavirus species-specificity prevents HPVs from infecting non-human species (Doorbar, 2016). Nevertheless, there are some animal PVs causing diseases in animal models that resemble the human situation.…”

Primary Cultures Derived From Bovine Papillomavirus-Infected Lesions As Model To Study Metabolic Deregulation

“…Although it is well stated that both HPV [9] and BPV promote DNA damages (mutations) that can lead to cancer initiation [10][11][12][13], there are few studies about the viral action in cell metabolism [5,[14][15][16]. This occurs due to the lack of attention given to in vitro models [17]. In this sense, since 2003, our group has demonstrated that primary cultures derived from BPV-infected lesions are useful model to understand the viral interaction with host chromatin [18].…”