{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:55:43Z","timestamp":1778604943269,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012649","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000}}],"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute, NIH","doi-asserted-by":"crossref","award":["1ZIASC010357"],"award-info":[{"award-number":["1ZIASC010357"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA47622"],"award-info":[{"award-number":["R01CA47622"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201708330003"],"award-info":[{"award-number":["201708330003"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Cottontail rabbit papillomavirus (CRPV), the first papillomavirus associated with tumor development, has been used as a powerful model to study papillomavirus pathogenesis for more than 90 years. However, lack of a comprehensive analysis of the CRPV transcriptome has impeded the understanding of CRPV biology and molecular pathogenesis. Here, we report the construction of a complete CRPV transcription map from Hershey CRPV-induced skin tumor tissues. By using RNA-seq in combination with long-reads PacBio Iso-seq, 5\u2032 and 3\u2032 RACE, primer-walking RT-PCR, Northern blot, and RNA <jats:italic>in situ<\/jats:italic> hybridization, we demonstrated that the CRPV genome transcribes its early and late RNA transcripts unidirectionally from at least five distinct major promoters (P) and polyadenylates its transcripts at two major polyadenylation (pA) sites. The viral early transcripts are primarily transcribed from three \u201cearly\u201d promoters, P<jats:sub>90<\/jats:sub>, P<jats:sub>156<\/jats:sub>, and P<jats:sub>907<\/jats:sub> and polyadenylated at nt 4368 by using an early polyadenylation signal (PAS) at nt 4351. Like other low-risk human papillomaviruses and animal papillomaviruses, CRPV E6 and E7 transcripts are transcribed from three separate early promoters. Transcripts from two \u201clate\u201d promoters, P<jats:sub>7525<\/jats:sub>, and P<jats:sub>1225<\/jats:sub>, utilize either an early PAS for E1^E4 or a late PAS at 7399 for L2 and L1 RNA polyadenylation at nt 7415 to express capsid L2 and L1 proteins respectively. By using the mapped four 5\u2032 splice sites and three 3\u2032 splice sites, CRPV RNA transcripts undergo extensive alternative splicing to produce more than 33 viral RNA isoforms for production of at least 12 viral proteins, some of which without codon optimization are expressible in rabbit RK13 and human HEK293T cells. The constructed full CRPV transcription map in this study for the first time will enhance our understanding of the structures and expressions of CRPV genes and their contribution to molecular pathogenesis and tumorigenesis.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012649","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T17:40:41Z","timestamp":1729878041000},"page":"e1012649","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The full transcription map of cottontail rabbit papillomavirus in tumor tissues"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-2406","authenticated-orcid":true,"given":"Pengfei","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2907-4583","authenticated-orcid":true,"given":"Vladimir","family":"Majerciak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8700-9937","authenticated-orcid":true,"given":"Jiafen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karla","family":"Balogh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie","family":"Cam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra","family":"Shearer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Lanza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil D.","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5547-7912","authenticated-orcid":true,"given":"Zhi-Ming","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"issue":"5","key":"ppat.1012649.ref001","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1084\/jem.58.5.607","article-title":"INFECTIOUS PAPILLOMATOSIS OF RABBITS: WITH A NOTE ON THE HISTOPATHOLOGY","volume":"58","author":"RE Shope","year":"1933","journal-title":"J Exp Med"},{"issue":"6","key":"ppat.1012649.ref002","doi-asserted-by":"crossref","first-page":"830","DOI":"10.3181\/00379727-32-7875","article-title":"Serial transmission of virus of infectious papillomatosis in domestic rabbits","volume":"32","author":"RE Shope","year":"1935","journal-title":"Proceedings of the Society for Experimental Biology and Medicine"},{"key":"ppat.1012649.ref003","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1084\/jem.60.6.701","article-title":"A virus-induced mammalian growth with characters of a tumor (the Shope rabbit papilloma): I. The growth on implantation within favorable hosts","volume":"60","author":"P Rous","year":"1934","journal-title":"J Exp Med"},{"key":"ppat.1012649.ref004","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1084\/jem.62.4.523","article-title":"The progression to carcinoma of virus-induced rabbit papilloma (Shope)","volume":"62","author":"P Rous","year":"1935","journal-title":"J Exp Med"},{"key":"ppat.1012649.ref005","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.3181\/00379727-128-33185","article-title":"Immunofluorescence studies of Shope papilloma virus in cottontail rabbit kidney tissue cultures","volume":"128","author":"T Osato","year":"1968","journal-title":"Proc Soc Exp Biol Med"},{"issue":"1773","key":"ppat.1012649.ref006","doi-asserted-by":"crossref","first-page":"20180294","DOI":"10.1098\/rstb.2018.0294","article-title":"The rabbit papillomavirus model: a valuable tool to study viral-host interactions","volume":"374","author":"NM 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