A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus

ABSTRACT Up to 95% of all anal cancers are associated with infection by human papillomavirus (HPV); however, no established preclinical model exists for high-grade anal disease and cancer mediated by a natural papillomavirus infection. To establish an infection-mediated model, we infected both immun...

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Autores principales:	Simon Blaine-Sauer, Myeong-Kyun Shin, Kristina A. Matkowskyj, Ella Ward-Shaw, Paul F. Lambert
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	DMBA HPV anal cancer infection mouse papillomavirus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/eb7208b007944495a91c104430d5ed0c
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spelling	oai:doaj.org-article:eb7208b007944495a91c104430d5ed0c2021-11-10T18:37:51ZA Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus10.1128/mBio.01611-212150-7511https://doaj.org/article/eb7208b007944495a91c104430d5ed0c2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01611-21https://doaj.org/toc/2150-7511ABSTRACT Up to 95% of all anal cancers are associated with infection by human papillomavirus (HPV); however, no established preclinical model exists for high-grade anal disease and cancer mediated by a natural papillomavirus infection. To establish an infection-mediated model, we infected both immunocompromised NSG and immunocompetent FVB/NJ mice with the recently discovered murine papillomavirus MmuPV1, with and without the additional cofactors of UV B radiation (UVB) and/or the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Infections were tracked via lavages and swabs for MmuPV1 DNA, and pathology was assessed at the endpoint. Tissues were analyzed for biomarkers of viral infection and papillomavirus-mediated disease, and the localization of viral infection was investigated using biomarkers to characterize the anal microanatomical zones. IMPORTANCE We show, for the first time, that MmuPV1 infection is sufficient to efficiently mediate high-grade squamous intraepithelial lesions in the anal tract of mice using the NSG immunocompromised strain and that MmuPV1, in combination with the chemical carcinogen DMBA, has carcinogenic potential. We further show that MmuPV1 is able to persist for up to 6 months in the anal tract of FVB/NJ mice irradiated with UVB and contributes to high-grade disease and cancer in an immunocompetent strain. We demonstrate that MmuPV1 preferentially localizes to the anal transition zone and that this localization is not an artifact of infection methodology. This study presents a valuable new preclinical model for studying papillomavirus-mediated anal disease driven by a natural infection.Simon Blaine-SauerMyeong-Kyun ShinKristina A. MatkowskyjElla Ward-ShawPaul F. LambertAmerican Society for MicrobiologyarticleDMBAHPVanal cancerinfectionmousepapillomavirusMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DMBA HPV anal cancer infection mouse papillomavirus Microbiology QR1-502
spellingShingle	DMBA HPV anal cancer infection mouse papillomavirus Microbiology QR1-502 Simon Blaine-Sauer Myeong-Kyun Shin Kristina A. Matkowskyj Ella Ward-Shaw Paul F. Lambert A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus
description	ABSTRACT Up to 95% of all anal cancers are associated with infection by human papillomavirus (HPV); however, no established preclinical model exists for high-grade anal disease and cancer mediated by a natural papillomavirus infection. To establish an infection-mediated model, we infected both immunocompromised NSG and immunocompetent FVB/NJ mice with the recently discovered murine papillomavirus MmuPV1, with and without the additional cofactors of UV B radiation (UVB) and/or the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Infections were tracked via lavages and swabs for MmuPV1 DNA, and pathology was assessed at the endpoint. Tissues were analyzed for biomarkers of viral infection and papillomavirus-mediated disease, and the localization of viral infection was investigated using biomarkers to characterize the anal microanatomical zones. IMPORTANCE We show, for the first time, that MmuPV1 infection is sufficient to efficiently mediate high-grade squamous intraepithelial lesions in the anal tract of mice using the NSG immunocompromised strain and that MmuPV1, in combination with the chemical carcinogen DMBA, has carcinogenic potential. We further show that MmuPV1 is able to persist for up to 6 months in the anal tract of FVB/NJ mice irradiated with UVB and contributes to high-grade disease and cancer in an immunocompetent strain. We demonstrate that MmuPV1 preferentially localizes to the anal transition zone and that this localization is not an artifact of infection methodology. This study presents a valuable new preclinical model for studying papillomavirus-mediated anal disease driven by a natural infection.
format	article
author	Simon Blaine-Sauer Myeong-Kyun Shin Kristina A. Matkowskyj Ella Ward-Shaw Paul F. Lambert
author_facet	Simon Blaine-Sauer Myeong-Kyun Shin Kristina A. Matkowskyj Ella Ward-Shaw Paul F. Lambert
author_sort	Simon Blaine-Sauer
title	A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus
title_short	A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus
title_full	A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus
title_fullStr	A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus
title_full_unstemmed	A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus
title_sort	novel model for papillomavirus-mediated anal disease and cancer using the mouse papillomavirus
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/eb7208b007944495a91c104430d5ed0c
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A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus

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