Recent advances in preclinical model systems for papillomaviruses

Abstract

Preclinical model systems to study multiple features of the papillomavirus life cycle have greatly aided our understanding of Human Papillomavirus (HPV) biology, disease progression and treatments. The challenge to studying HPV in hosts is that HPV along with most PVs are both species and tissue restricted. Thus, fundamental properties of HPV viral proteins can be assessed in specialized cell culture systems but host responses that involve innate immunity and host restriction factors requires preclinical surrogate models. Fortunately, there are several well-characterized and new animal models of papillomavirus infections that are available to the PV research community. Old models that continue to have value include canine, bovine and rabbit PV models and new rodent models are in place to better assess host-virus interactions. Questions arise as to the strengths and weaknesses of animal PV models for HPV disease and how accurately these preclinical models predict malignant progression, vaccine efficacy and therapeutic control of HPV-associated disease. In this review, we examine current preclinical models and highlight the strengths and weaknesses of the various models as well as provide an update on new opportunities to study the numerous unknowns that persist in the HPV research field.

The rabbit papillomavirus model: a valuable tool to study viral–host interactions

“…Intriguingly, codonmodified E6 synergized with codon-modified E7 and induced early cancer development in domestic rabbits [52]. Some of these constructs, by contrast, showed higher regression rates than those of the wild-type [55]. These findings suggest that synonymous codon modifications can alter the immunogenicity of the virus and lead to either rapid progression or eventual regression depending upon the changes made.…”

“…The SfPV1/rabbit papillomavirus model induces infection with long-term persistence and malignant progression of lesions both consistently and reproducibly. Eighty years of studies with this unique model have proved it to be one of the best surrogate models for studying high-risk HPV infection [55,100]. Over the past several decades, we and others have generated a large panel of mutants to aid in the study of the pathogenesis of papillomavirus [55].…”

“…Eighty years of studies with this unique model have proved it to be one of the best surrogate models for studying high-risk HPV infection [55,100]. Over the past several decades, we and others have generated a large panel of mutants to aid in the study of the pathogenesis of papillomavirus [55]. These mutant constructs will allow us to dissect the function of different genes and their role in the pathogenesis of papillomavirusassociated skin infections.…”

Contribution of the swine model in the study of human sexually transmitted infections

“…The species-specific nature of papillomaviruses has prevented adaptation of authentic HPV infections to experimental animal models. However, significant discoveries in the understanding of papillomaviruses pathogenesis have been carried out using cattle, dog, NHP, and rabbit (Sylvilagus floridanus and Oryctolagus cuniculus) natural models (Christensen et al, 2017).…”

“…More recently new models have been developed in mice and multi-mammate rats (Christensen et al, 2017). Anogenital lesions including neoplasia are described in humans and are associated predominantly to HPV-16 and HPV-18 (Howley et al, 2013).…”