A Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract

ABSTRACT Papillomaviruses exhibit species-specific tropism, thereby limiting understanding and research of several aspects of HPV infection and carcinogenesis. The discovery of a murine papillomavirus (MmuPV1) provides the opportunity to study papillomavirus infections in a tractable, in vivo labora...

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Autores principales:	Megan E. Spurgeon, Aayushi Uberoi, Stephanie M. McGregor, Tao Wei, Ella Ward-Shaw, Paul F. Lambert
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	cancer cervix infectious disease mouse papillomavirus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1c489332ada44e738485519c743d7fc2
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spelling	oai:doaj.org-article:1c489332ada44e738485519c743d7fc22021-11-15T15:55:25ZA Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract10.1128/mBio.00180-192150-7511https://doaj.org/article/1c489332ada44e738485519c743d7fc22019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00180-19https://doaj.org/toc/2150-7511ABSTRACT Papillomaviruses exhibit species-specific tropism, thereby limiting understanding and research of several aspects of HPV infection and carcinogenesis. The discovery of a murine papillomavirus (MmuPV1) provides the opportunity to study papillomavirus infections in a tractable, in vivo laboratory model. MmuPV1 infects and causes disease in the cutaneous epithelium, as well as the mucosal epithelia of the oral cavity and anogenital tract. In this report, we describe a murine model of MmuPV1 infection and neoplastic disease in the female reproductive tracts of wild-type immunocompetent FVB mice. Low-grade dysplastic lesions developed in reproductive tracts of FVB mice infected with MmuPV1 for 4 months, and mice infected for 6 months developed significantly worse disease, including squamous cell carcinoma (SCC). We also tested the contribution of estrogen and/or UV radiation (UVR), two cofactors we previously identified as being involved in papillomavirus-mediated disease, to cervicovaginal disease. Similar to HPV16 transgenic mice, exogenous estrogen treatment induced high-grade precancerous lesions in the reproductive tracts of MmuPV1-infected mice by 4 months and together with MmuPV1 efficiently induced SCC by 6 months. UV radiation and exogenous estrogen cooperated to promote carcinogenesis in MmuPV1-infected mice. This murine infection model represents the first instance of de novo papillomavirus-mediated carcinogenesis in the female reproductive tract of wild-type mice resulting from active virus infection and is also the first report of the female hormone estrogen contributing to this process. This model will provide an additional platform for fundamental studies on papillomavirus infection, cervicovaginal disease, and the role of cellular cofactors during papillomavirus-induced carcinogenesis. IMPORTANCE Tractable and efficient models of papillomavirus-induced pathogenesis are limited due to the strict species-specific and tissue-specific tropism of these viruses. Here, we report a novel preclinical murine model of papillomavirus-induced cervicovaginal disease in wild-type, immunocompetent mice using the recently discovered murine papillomavirus, MmuPV1. In this model, MmuPV1 establishes persistent viral infections in the mucosal epithelia of the female reproductive tract, a necessary component needed to accurately mimic HPV-mediated neoplastic disease in humans. Persistent MmuPV1 infections were able to induce progressive neoplastic disease and carcinogenesis, either alone or in combination with previously identified cofactors of papillomavirus-induced disease. This new model will provide a much-needed platform for basic and translational studies on both papillomavirus infection and associated disease in immunocompetent mice.Megan E. SpurgeonAayushi UberoiStephanie M. McGregorTao WeiElla Ward-ShawPaul F. LambertAmerican Society for Microbiologyarticlecancercervixinfectious diseasemousepapillomavirusMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer cervix infectious disease mouse papillomavirus Microbiology QR1-502
spellingShingle	cancer cervix infectious disease mouse papillomavirus Microbiology QR1-502 Megan E. Spurgeon Aayushi Uberoi Stephanie M. McGregor Tao Wei Ella Ward-Shaw Paul F. Lambert A Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract
description	ABSTRACT Papillomaviruses exhibit species-specific tropism, thereby limiting understanding and research of several aspects of HPV infection and carcinogenesis. The discovery of a murine papillomavirus (MmuPV1) provides the opportunity to study papillomavirus infections in a tractable, in vivo laboratory model. MmuPV1 infects and causes disease in the cutaneous epithelium, as well as the mucosal epithelia of the oral cavity and anogenital tract. In this report, we describe a murine model of MmuPV1 infection and neoplastic disease in the female reproductive tracts of wild-type immunocompetent FVB mice. Low-grade dysplastic lesions developed in reproductive tracts of FVB mice infected with MmuPV1 for 4 months, and mice infected for 6 months developed significantly worse disease, including squamous cell carcinoma (SCC). We also tested the contribution of estrogen and/or UV radiation (UVR), two cofactors we previously identified as being involved in papillomavirus-mediated disease, to cervicovaginal disease. Similar to HPV16 transgenic mice, exogenous estrogen treatment induced high-grade precancerous lesions in the reproductive tracts of MmuPV1-infected mice by 4 months and together with MmuPV1 efficiently induced SCC by 6 months. UV radiation and exogenous estrogen cooperated to promote carcinogenesis in MmuPV1-infected mice. This murine infection model represents the first instance of de novo papillomavirus-mediated carcinogenesis in the female reproductive tract of wild-type mice resulting from active virus infection and is also the first report of the female hormone estrogen contributing to this process. This model will provide an additional platform for fundamental studies on papillomavirus infection, cervicovaginal disease, and the role of cellular cofactors during papillomavirus-induced carcinogenesis. IMPORTANCE Tractable and efficient models of papillomavirus-induced pathogenesis are limited due to the strict species-specific and tissue-specific tropism of these viruses. Here, we report a novel preclinical murine model of papillomavirus-induced cervicovaginal disease in wild-type, immunocompetent mice using the recently discovered murine papillomavirus, MmuPV1. In this model, MmuPV1 establishes persistent viral infections in the mucosal epithelia of the female reproductive tract, a necessary component needed to accurately mimic HPV-mediated neoplastic disease in humans. Persistent MmuPV1 infections were able to induce progressive neoplastic disease and carcinogenesis, either alone or in combination with previously identified cofactors of papillomavirus-induced disease. This new model will provide a much-needed platform for basic and translational studies on both papillomavirus infection and associated disease in immunocompetent mice.
format	article
author	Megan E. Spurgeon Aayushi Uberoi Stephanie M. McGregor Tao Wei Ella Ward-Shaw Paul F. Lambert
author_facet	Megan E. Spurgeon Aayushi Uberoi Stephanie M. McGregor Tao Wei Ella Ward-Shaw Paul F. Lambert
author_sort	Megan E. Spurgeon
title	A Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract
title_short	A Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract
title_full	A Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract
title_fullStr	A Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract
title_full_unstemmed	A Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract
title_sort	novel <italic toggle="yes">in vivo</italic> infection model to study papillomavirus-mediated disease of the female reproductive tract
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/1c489332ada44e738485519c743d7fc2
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A Novel <italic toggle="yes">In Vivo</italic> Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract

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