title: Life cycle heterogeneity in animal models of human papillomavirus-associated disease.
abstract: Animal papillomaviruses are widely used as models to study papillomavirus infection in humans despite differences in genome organization and tissue tropism. Here, we have investigated the extent to which animal models of papillomavirus infection resemble human disease by comparing the life cycles of 10 different papillomavirus types. Three phases in the life cycles of all viruses were apparent using antibodies that distinguish between early events, the onset of viral genome amplification, and the expression of capsid proteins. The initiation of these phases follows a highly ordered pattern that appears important for the production of virus particles. The viruses examined included canine oral papillomavirus, rabbit oral papillomavirus (ROPV), cottontail rabbit papillomavirus (CRPV), bovine papillomavirus type 1, and human papillomavirus types 1, 2, 11, and 16. Each papillomavirus type showed a distinctive gene expression pattern that could be explained in part by differences in tissue tropism, transmission route, and persistence. As the timing of life cycle events affects the accessibility of viral antigens to the immune system, the ideal model system should resemble human mucosal infection if vaccine design is to be effective. Of the model systems examined here, only ROPV had a tissue tropism and a life cycle organization that resembled those of the human mucosal types. ROPV appears most appropriate for studies of the life cycles of mucosal papillomavirus types and for the development of prophylactic vaccines. The persistence of abortive infections caused by CRPV offers advantages for the development of therapeutic vaccines.
authors.affiliation: National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Woei Ling
authors.initials: WL
authors.lastname: Peh
authors.forename: Kate
authors.initials: K
authors.lastname: Middleton
authors.forename: Neil
authors.initials: N
authors.lastname: Christensen
authors.forename: Philip
authors.initials: P
authors.lastname: Nicholls
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Egawa
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.forename: Janet
authors.initials: J
authors.lastname: Brandsma
authors.forename: Alan
authors.initials: A
authors.lastname: Percival
authors.forename: Jon
authors.initials: J
authors.lastname: Lewis
authors.forename: Wen Jun
authors.initials: WJ
authors.lastname: Liu
authors.forename: John
authors.initials: J
authors.lastname: Doorbar
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D052688:Bovine papillomavirus 1 / Q000378:metabolism / Q000502:physiology*; D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins; D012777:Cottontail rabbit papillomavirus / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D005814:Genes, Viral; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae / Q000378:metabolism / Q000502:physiology*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D011817:Rabbits; D013997:Time Factors; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015678:Viral Structural Proteins / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; C094776:L1 protein, Human papillomavirus type 11; C097166:L1 protein, canine oral papillomavirus; C073505:L1 protein, cottontail rabbit papillomavirus; D009856:Oncogene Proteins, Viral; D015678:Viral Structural Proteins; C069119:oncogene protein E4, Human papillomavirus type 16; C067860:oncogene protein E4, type 11, Human papillomavirus