title: Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan.
abstract: Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection, and virtually all cases of cervical cancer are attributable to infection by a subset of HPVs (reviewed in ref. 1). Despite the high incidence of HPV infection and the recent development of a prophylactic vaccine that confers protection against some HPV types, many features of HPV infection are poorly understood. It remains worthwhile to consider other interventions against genital HPVs, particularly those that target infections not prevented by the current vaccine. However, productive papillomavirus infection is species- and tissue-restricted, and traditional models use animal papillomaviruses that infect the skin or oral mucosa. Here we report the development of a mouse model of cervicovaginal infection with HPV16 that recapitulates the establishment phase of papillomavirus infection. Transduction of a reporter gene by an HPV16 pseudovirus was characterized by histology and quantified by whole-organ, multispectral imaging. Disruption of the integrity of the stratified or columnar genital epithelium was required for infection, which occurred after deposition of the virus on the basement membrane underlying basal keratinocytes. A widely used vaginal spermicide, nonoxynol-9 (N-9), greatly increased susceptibility to infection. In contrast, carrageenan, a polysaccharide present in some vaginal lubricants, prevented infection even in the presence of N-9, suggesting that carrageenan might serve as an effective topical HPV microbicide.
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4263, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Roberts
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Buck
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Thompson
authors.forename: Rhonda
authors.initials: R
authors.lastname: Kines
authors.forename: Marcelino
authors.initials: M
authors.lastname: Bernardo
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
mesh_terms: D000818:Animals; D002213:Capsid / Q000502:physiology; D002351:Carrageenan / Q000494:pharmacology*; D005260:Female; D052162:Human papillomavirus 16 / Q000502:physiology*; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology / Q000821:virology; D017137:Nonoxynol / Q000494:pharmacology*; D030361:Papillomavirus Infections / Q000517:prevention & control / Q000635:transmission* / Q000821:virology; D013089:Spermatocidal Agents / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects / Q000821:virology
chemical_list: D013089:Spermatocidal Agents; D017137:Nonoxynol; D002351:Carrageenan