{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:11:22Z","timestamp":1780524682393,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Erasmus+ program","award":["2158-60-03-19-19"],"award-info":[{"award-number":["2158-60-03-19-19"]}]},{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["P3-00083"],"award-info":[{"award-number":["P3-00083"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human papillomavirus type 159 (HPV159) was identified in an anal swab sample and preliminarily genetically characterized by our group in 2012. Here we present a detailed molecular in silico analysis that showed that the HPV159 viral genome is 7443 bp in length and divided into five early and two late genes, with conserved functional domains and motifs, and a non-coding long control region (LCR) with significant regulatory sequences that allow the virus to complete its life cycle and infect novel host cells. HPV159, clustering into the cutaneotropic Betapapillomavirus (Beta-PV) genus, is phylogenetically most similar to HPV9, forming an individual phylogenetic group in the viral species Beta-2. After testing a large representative collection of clinical samples with HPV159 type-specific RT-PCR, in addition to the anal canal from which the first HPV159 isolate was obtained, HPV159 was further detected in other muco-cutaneous (4\/181, 2.2%), mucosal (22\/764, 2.9%), and cutaneous (14\/554, 2.5%) clinical samples, suggesting its extensive tissue tropism. However, because very low HPV159 viral loads were estimated in the majority of positive samples, it seemed that HPV159 mainly caused clinically insignificant infections of the skin and mucosa. Using newly developed, highly sensitive HPV159-specific nested PCRs, two additional HPV159 LCR viral variants were identified. Nevertheless, all HPV159 mutations were demonstrated outside important functional domains of the LCR, suggesting that the HPV159 viral variants were most probably not pathogenically different. This complete molecular characterization of HPV159 enhances our knowledge of the genome characteristics, tissue tropism, and phylogenetic diversity of Beta-PVs that infect humans.<\/jats:p>","DOI":"10.3390\/v13081668","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T23:19:33Z","timestamp":1629760773000},"page":"1668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Molecular Characterization of Human Papillomavirus Type 159 (HPV159)"],"prefix":"10.3390","volume":"13","author":[{"given":"Iva","family":"Markovi\u0107","sequence":"first","affiliation":[{"name":"Division of Molecular Biology, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka Cesta 54, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-0309","authenticated-orcid":false,"given":"Lea","family":"Ho\u0161njak","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zalo\u0161ka Cesta 4, 1105 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-7644","authenticated-orcid":false,"given":"Katja","family":"Seme","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zalo\u0161ka Cesta 4, 1105 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3216-7564","authenticated-orcid":false,"given":"Mario","family":"Poljak","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zalo\u0161ka Cesta 4, 1105 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.jcv.2004.12.006","article-title":"The papillomavirus life cycle","volume":"32","author":"Doorbar","year":"2005","journal-title":"J. Clin. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.meegid.2013.03.011","article-title":"Taxonomy and phylogeny of papillomaviruses: An overview and recent development","volume":"18","author":"Bernard","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.cmi.2015.05.011","article-title":"Molecular methods for identification and characterization of novel papillomaviruses","volume":"21","author":"Kocjan","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virol.2004.03.033","article-title":"Classification of papillomaviruses","volume":"324","author":"Fauquet","year":"2004","journal-title":"Virology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.virol.2013.04.023","article-title":"Cross-roads in the classification of papillomaviruses","volume":"445","year":"2013","journal-title":"Virology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.virusres.2016.11.013","article-title":"The biology of beta human papillomaviruses","volume":"231","author":"Tommasino","year":"2017","journal-title":"Virus Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"D499","DOI":"10.1093\/nar\/gkw879","article-title":"The Papillomavirus Episteme: A major update to the papillomavirus sequence database","volume":"45","author":"Li","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.virol.2013.05.012","article-title":"Evolution of Papillomaviridae","volume":"445","year":"2013","journal-title":"Virology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1155\/2007\/613150","article-title":"Papillomavirus life cycle organization and biomarker selection","volume":"23","author":"Doorbar","year":"2007","journal-title":"Dis. Markers"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/rmv.605","article-title":"Molecular mechanisms of cervical carcinogenesis by high-risk human papillomaviruses: Novel functions of E6 and E7 oncoproteins","volume":"19","author":"Yugawa","year":"2009","journal-title":"Rev. Med. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7888","DOI":"10.1038\/sj.onc.1204860","article-title":"Biological activities and molecular targets of the human papillomavirus E7 protein","volume":"20","author":"Munger","year":"2001","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1042\/CS20050369","article-title":"Molecular biology of human papillomavirus infection and cervical cancer","volume":"5","author":"Doorbar","year":"2006","journal-title":"Clin. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/path.4425","article-title":"Human Beta-papillomavirus infection and keratinocyte carcinomas","volume":"235","author":"Quint","year":"2015","journal-title":"J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1128\/JCM.41.6.2509-2514.2003","article-title":"General acquisition of human papillomavirus infections of skin occurs in early infancy","volume":"41","author":"Antonsson","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S0140-6736(84)92221-9","article-title":"Cancer, warts, and sunshine in renal transplant patients. A case-control study","volume":"1","author":"Boyle","year":"1984","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1006\/scbi.1999.0143","article-title":"Papillomaviruses in non-melanoma skin cancer: Epidemiological aspects","volume":"9","author":"Kiviat","year":"1999","journal-title":"Semin. Cancer Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00298-13","DOI":"10.1128\/genomeA.00298-13","article-title":"Complete genome sequence of a novel human Betapapillomavirus, HPV-159","volume":"1","author":"Kocjan","year":"2013","journal-title":"Genome Announc."},{"key":"ref_18","first-page":"203","article-title":"Signal scan: A computer program that scans DNA sequences for eukaryotic transcriptional elements","volume":"7","author":"Prestridge","year":"1991","journal-title":"Comput. Appl. Biosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1074\/jbc.M508455200","article-title":"Structure of the human Papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor","volume":"281","author":"Liu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1093\/nar\/26.11.2740","article-title":"Computational approaches to identify leucine zippers","volume":"26","author":"Rivals","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/ijc.21920","article-title":"Subtype HPV38b[FA125] demonstrates heterogeneity of human papillomavirus type 38","volume":"119","author":"Hazard","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.meegid.2004.05.009","article-title":"Distribution of human papillomavirus genotypes in plucked eyebrow hairs from Slovenian males with genital warts","volume":"5","author":"Kocjan","year":"2005","journal-title":"Infect. Genet. Evol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"58","DOI":"10.2144\/000112499","article-title":"Improved DNA sequencing quality and efficiency using an optimized fast cycle sequencing protocol","volume":"43","author":"Platt","year":"2007","journal-title":"BioTechniques"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4993","DOI":"10.1128\/JVI.78.10.4993-4998.2004","article-title":"A sequence-independent strategy for detection and cloning of circular DNA virus genomes by using multiply primed rolling-circle amplification","volume":"78","author":"Rector","year":"2004","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/1476-4598-10-140","article-title":"Papillomavirus E5: The smallest oncoprotein with many functions","volume":"10","author":"Venuti","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1128\/JVI.02068-08","article-title":"Evolutionary dynamics of variant genomes of human papillomavirus types 18, 45 and 97","volume":"88","author":"Chen","year":"2009","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.virol.2013.07.020","article-title":"The E1 proteins","volume":"445","author":"Bergvall","year":"2013","journal-title":"Virology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.virol.2013.06.006","article-title":"The papillomavirus E2 proteins","volume":"445","author":"McBride","year":"2013","journal-title":"Virology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mrrev.2016.07.002","article-title":"Human papillomavirus molecular biology","volume":"772","author":"Harden","year":"2017","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1128\/MMBR.68.2.362-372.2004","article-title":"Pathogenesis of human papillomaviruses in differentiating epithelia","volume":"68","author":"Longworth","year":"2004","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0065-3527(08)00404-1","article-title":"Replication and partitioning of papillomavirus genomes","volume":"72","author":"McBride","year":"2008","journal-title":"Adv. Virus Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1515\/hsz-2017-0113","article-title":"Mechanisms and strategies of papillomavirus replication","volume":"398","author":"McBride","year":"2017","journal-title":"Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1099\/vir.0.006544-0","article-title":"Macaca fascicularis papillomavirus type 1: A non-human primate betapapillomavirus causing rapidly progressive hand and foot papillomatosis","volume":"90","author":"Joh","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1099\/vir.0.048157-0","article-title":"Identification of human papillomavirus type 156, the prototype of a new human gammapapillomavirus species, by a generic and highly sensitive PCR strategy for long DNA fragments","volume":"94","author":"Chouhy","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.virol.2013.07.008","article-title":"The E4 protein; structure, function and patterns of expression","volume":"445","author":"Doorbar","year":"2013","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.virol.2008.11.017","article-title":"Papillomavirus E6 proteins","volume":"384","author":"Howie","year":"2009","journal-title":"Virology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.bbagrm.2019.01.001","article-title":"Hallmarks of HPV carcinogenesis: The role of E6, E7 and E5 oncoproteins in cellular malignancy","volume":"1862","author":"Estevao","year":"2019","journal-title":"Biochim. Biophys. Acta Gene Regul. Mech."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.virol.2013.04.013","article-title":"The papillomavirus E7 proteins","volume":"445","author":"Roman","year":"2013","journal-title":"Virology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.1093\/emboj\/cdf494","article-title":"Atomic model of the papillomavirus capsid","volume":"21","author":"Modis","year":"2002","journal-title":"EMBO J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1128\/jvi.61.9.2793-2799.1987","article-title":"Identification of proteins encoded by the L1 and L2 open reading frames of human papillomavirus","volume":"61","author":"Doorbar","year":"1987","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1099\/0022-1317-70-5-1133","article-title":"Identification of L2 open reading frame gene products of bovine papillomavirus type 1 using monoclonal antibodies","volume":"70","author":"Jin","year":"1989","journal-title":"J. Gen. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.virol.2013.04.017","article-title":"L2, the minor capsid protein of papillomavirus","volume":"445","author":"Wang","year":"2013","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5190","DOI":"10.1128\/JVI.02726-07","article-title":"Arrangement of L2 within the papillomavirus capsid","volume":"82","author":"Buck","year":"2008","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/1743-422X-5-150","article-title":"Evolutionary and structural analyses of alpha-papillomavirus capsid proteins yields novel insights into L2 structure and interaction with L1","volume":"5","author":"Lowe","year":"2008","journal-title":"Virol. J."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kovanda, A., Kocjan, B.J., Poto\u010dnik, M., and Poljak, M. (2011). Characterization of a novel cutaneous human papillomavirus genotype HPV-125. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022414"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pvr.2017.02.002","article-title":"Prevalence of cutaneous beta and gamma human papillomaviruses in the anal canal of men who have sex with women","volume":"3","author":"Smelov","year":"2017","journal-title":"Papillomavirus Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jcv.2014.07.009","article-title":"Betapapillomaviruses in the anal canal of HIV positive and HIV negative men who have sex with men","volume":"61","author":"Mlakar","year":"2014","journal-title":"J. Clin. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/infdis\/jir383","article-title":"The oral cavity contains abundant known and novel human papillomaviruses from the Betapapillomavirus and Gammapapillomavirus genera","volume":"204","author":"Bottalico","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jcv.2013.10.028","article-title":"Characterization of three novel human papillomavirus types isolated from oral rinse samples of healthy individuals","volume":"59","author":"Martin","year":"2014","journal-title":"J. Clin. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1099\/vir.0.82732-0","article-title":"Betapapillomaviruses frequently persist in the skin of healthy individuals","volume":"88","author":"Struijk","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/j.1365-2133.2009.09297.x","article-title":"High viral load of human wart-associated papillomaviruses (PV) but not beta-PV in cutaneous warts independent of immunosuppression","volume":"161","author":"Meyer","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1093\/infdis\/jit326","article-title":"The nasal mucosa contains a large spectrum of human papillomavirus types from the betapapillomavirus and gammapapillomavirus genera","volume":"208","author":"Forslund","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.virol.2013.04.024","article-title":"Broad HPV distribution in the genital region of men from the HPV infection in men (HIM) study","volume":"443","author":"Sichero","year":"2013","journal-title":"Virology"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1668\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:49:55Z","timestamp":1760165395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":54,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["v13081668"],"URL":"https:\/\/doi.org\/10.3390\/v13081668","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,23]]}}}