{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:11:35Z","timestamp":1773706295594,"version":"3.50.1"},"reference-count":151,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T00:00:00Z","timestamp":1662249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01 CA47622"],"award-info":[{"award-number":["R01 CA47622"]}]},{"name":"National Cancer Institute","award":["HHSN272201000020I"],"award-info":[{"award-number":["HHSN272201000020I"]}]},{"name":"NIH","award":["R01 CA47622"],"award-info":[{"award-number":["R01 CA47622"]}]},{"name":"NIH","award":["HHSN272201000020I"],"award-info":[{"award-number":["HHSN272201000020I"]}]},{"name":"Jake Gittlen Memorial Golf Tournament","award":["R01 CA47622"],"award-info":[{"award-number":["R01 CA47622"]}]},{"name":"Jake Gittlen Memorial Golf Tournament","award":["HHSN272201000020I"],"award-info":[{"award-number":["HHSN272201000020I"]}]},{"name":"Department of Pathology and Laboratory Medicine, Penn State College of Medicine","award":["R01 CA47622"],"award-info":[{"award-number":["R01 CA47622"]}]},{"name":"Department of Pathology and Laboratory Medicine, Penn State College of Medicine","award":["HHSN272201000020I"],"award-info":[{"award-number":["HHSN272201000020I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Approximately 5% of all human cancers are attributable to human papillomavirus (HPV) infections. HPV-associated diseases and cancers remain a substantial public health and economic burden worldwide despite the availability of prophylactic HPV vaccines. Current diagnosis and treatments for HPV-associated diseases and cancers are predominantly based on cell\/tissue morphological examination and\/or testing for the presence of high-risk HPV types. There is a lack of robust targets\/markers to improve the accuracy of diagnosis and treatments. Several naturally occurring animal papillomavirus models have been established as surrogates to study HPV pathogenesis. Among them, the Cottontail rabbit papillomavirus (CRPV) model has become known as the gold standard. This model has played a pivotal role in the successful development of vaccines now available to prevent HPV infections. Over the past eighty years, the CRPV model has been widely applied to study HPV carcinogenesis. Taking advantage of a large panel of functional mutant CRPV genomes with distinct, reproducible, and predictable phenotypes, we have gained a deeper understanding of viral\u2013host interaction during tumor progression. In recent years, the application of genome-wide RNA-seq analysis to the CRPV model has allowed us to learn and validate changes that parallel those reported in HPV-associated cancers. In addition, we have established a selection of gene-modified rabbit lines to facilitate mechanistic studies and the development of novel therapeutic strategies. In the current review, we summarize some significant findings that have advanced our understanding of HPV pathogenesis and highlight the implication of the development of novel gene-modified rabbits to future mechanistic studies.<\/jats:p>","DOI":"10.3390\/v14091964","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T20:50:27Z","timestamp":1662670227000},"page":"1964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-4051","authenticated-orcid":false,"given":"Nancy M.","family":"Cladel","sequence":"first","affiliation":[{"name":"The Jake Gittlen Laboratories for Cancer Research, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA"},{"name":"Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-2878","authenticated-orcid":false,"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuwen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-2406","authenticated-orcid":false,"given":"Pengfei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Immunology, Department of Microbiology & Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil D.","family":"Christensen","sequence":"additional","affiliation":[{"name":"The Jake Gittlen Laboratories for Cancer Research, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA"},{"name":"Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"},{"name":"Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5547-7912","authenticated-orcid":false,"given":"Zhi-Ming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8700-9937","authenticated-orcid":false,"given":"Jiafen","family":"Hu","sequence":"additional","affiliation":[{"name":"The Jake Gittlen Laboratories for Cancer Research, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA"},{"name":"Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nrc.2018.13","article-title":"Opportunities and challenges for human papillomavirus vaccination in cancer","volume":"18","author":"Roden","year":"2018","journal-title":"Nat. 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