{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:16:46Z","timestamp":1781885806221,"version":"3.54.5"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["MPY1372\/2012"],"award-info":[{"award-number":["MPY1372\/2012"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["MPY 434\/2021"],"award-info":[{"award-number":["MPY 434\/2021"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Since human herpesvirus 8 (HHV-8) infection may be underestimated and HHV-8 subtype circulation in Spain remains unknown, a molecular epidemiologic study is highly desirable.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Objectives<\/jats:title><jats:p>This study aimed to analyse HHV-8 subtype diversity and their distribution in Spain.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Study design<\/jats:title><jats:p>The study included 142 HHV-8 infected patients. A nested PCR was developed in order to permit Sanger sequencing of HHV-8 K1 ORF directly from clinical samples received at the CNM from 2013 to 2021. Phylogenetic characterization was performed.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Results<\/jats:title><jats:p>Genotypes A and C comprised 55.6% and 42.3% of strains. Regarding subtypes, 25.4% of strains were C3, 19.7% were A3, 14.1% were A5, and C2, A1, A4, C1, A2, C7 were 11.3%, 11.3%, 8.5%, 4.2%, 2.1% and 1.4%, respectively. Subtype E1, E2 and B1 were found in only one patient each (0.7%). The Madrid region accounted for 52.1% of patients and showed a significantly different subtype distribution compared to the others (P = 0.018). Subtypes B1, E1, and E2 were observed to appear sporadically, although overall genotypes A and subtype C3 remained the most frequent and unwavering. Subtype A3 presented the highest diversity as displayed by the highest number of clusters in phylogenetic analysis. Non-significant differences in viral loads between genotypes were found, but significantly higher viral loads in subtype C2 compared to subtype C3 was found, while no significant subtype differences were observed between subtypes within genotype A. Infections with HHV-8 were detected in 94 (66.2%) patients without KS and compared to patients with KS non-significant differences in subtype distribution were found.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Conclusions<\/jats:title><jats:p>Subtype prevalence and regional distribution followed a similar pattern compared to other western European countries. Our study is the first to report HHV-8 subtypes E1 and E2 circulating in Europe that might be reflective of migration of population from Caribbean countries. Our study suggests that infection by HHV-8 is underestimated, and wider screening should be recommended for risk groups.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0274058","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T17:33:38Z","timestamp":1666719218000},"page":"e0274058","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular epidemiology of Kaposi sarcoma virus in Spain"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1537-3830","authenticated-orcid":true,"given":"Inmaculada","family":"G\u00f3mez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Dolores","family":"P\u00e9rez-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1298-3089","authenticated-orcid":true,"given":"David","family":"Tarrag\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"pone.0274058.ref001","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.canlet.2011.02.006","article-title":"Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma","volume":"305","author":"T.S. Uldrick","year":"2011","journal-title":"Cancer Lett"},{"issue":"80-","key":"pone.0274058.ref002","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1126\/science.7997879","article-title":"Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi\u2019s sarcoma","volume":"266","author":"Y. Chang","year":"1994","journal-title":"Science"},{"key":"pone.0274058.ref003","first-page":"15","volume-title":"Epigenetic regulation of gammaherpesviruses: A focus on Kaposi\u2019s sarcoma-associated Herpesvirus (KSHV\/HHV-8), in: Epigenetics Hum","author":"R. Poudyal","year":"2017"},{"key":"pone.0274058.ref004","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1006\/viro.2000.0629","article-title":"Molecular Epidemiology of Human Herpesvirus 8 in Africa: Both B and A5 K1 Genotypes, as Well as the M and P Genotypes of K14.1\/K15 Loci, Are Frequent and Widespread","volume":"278","author":"V. Lacoste","year":"2000","journal-title":"Virology"},{"key":"pone.0274058.ref005","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/jmv.24328","article-title":"Genetic diversity of HHV8 subtypes in South Africa: A5 subtype is associated with extensive disease in AIDS-KS, J","volume":"88","author":"T. Isaacs","year":"2016","journal-title":"Med. Virol"},{"key":"pone.0274058.ref006","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1128\/JVI.73.5.4156-4170.1999","article-title":"High-Level Variability in the ORF-K1 Membrane Protein Gene at the Left End of the Kaposi\u2019s Sarcoma-Associated Herpesvirus Genome Defines Four Major Virus Subtypes and Multiple Variants or Clades in Different Human Populations, J","volume":"73","author":"J.-C. Zong","year":"1999","journal-title":"Virol"},{"key":"pone.0274058.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcv.2007.06.012","article-title":"Reflections on the interpretation of heterogeneity and strain differences based on very limited PCR sequence data from Kaposi\u2019s sarcoma-associated herpesvirus genomes, J","volume":"40","author":"J.C. Zong","year":"2007","journal-title":"Clin. Virol"},{"key":"pone.0274058.ref008","doi-asserted-by":"crossref","first-page":"12299","DOI":"10.1128\/JVI.01712-15","article-title":"Whole-Genome Sequencing of Kaposi\u2019s Sarcoma-Associated Herpesvirus from Zambian Kaposi\u2019s Sarcoma Biopsy Specimens Reveals Unique Viral Diversity, J","volume":"89","author":"L.N. Olp","year":"2015","journal-title":"Virol"},{"key":"pone.0274058.ref009","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1006\/scbi.1998.0116","article-title":"KSHV strains: the origins and global spread of the virus, Semin","volume":"9","author":"G.S. Hayward","year":"1999","journal-title":"Cancer Biol"},{"key":"pone.0274058.ref010","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1007\/s00705-017-3467-1","article-title":"Was Kaposi\u2019s sarcoma-associated herpesvirus introduced into China via the ancient Silk Road?","volume":"162","author":"Z. Liu","year":"2017","journal-title":"An evolutionary perspective, Arch. Virol"},{"key":"pone.0274058.ref011","first-page":"540","volume":"29","author":"S.M. Marashi","year":"2018","journal-title":"Human herpesvirus 8 DNA detection and variant analysis in patients with multiple sclerosis, VirusDisease 2018 294"},{"key":"pone.0274058.ref012","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1386-6532(01)00205-0","article-title":"Genotypic analysis at multiple loci across Kaposi\u2019s sarcoma herpesvirus (KSHV) DNA molecules: clustering patterns, novel variants and chimerism, J","volume":"23","author":"J. Zong","year":"2002","journal-title":"Clin. Virol"},{"key":"pone.0274058.ref013","doi-asserted-by":"crossref","first-page":"e12278","DOI":"10.1111\/jicd.12278","article-title":"No detectable human herpesvirus-8 oral shedding in seronegative-healthy, immunocompetent individuals from non-endemic regions for Kaposi\u2019s sarcoma: A pilot study, J","volume":"9","author":"T.R. Tozetto-Mendoza","year":"2018","journal-title":"Investig. Clin. Dent"},{"key":"pone.0274058.ref014","first-page":"1","article-title":", Update of the global distribution of human gammaherpesvirus 8 genotypes, Sci","volume":"11","author":"A. de Oliveira Lopes","year":"2021","journal-title":"Reports 2021 111"},{"issue":"8","key":"pone.0274058.ref015","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1093\/infdis\/jiaa180","article-title":"New Kaposi\u2019s sarcoma-associated herpesvirus variant in men who have sex with men associated with severe pathologies","volume":"222","author":"A Jary","year":"2020","journal-title":"J Infect Dis"},{"key":"pone.0274058.ref016","first-page":"e5291","article-title":"Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma: Is genotype B associated with better prognosis of AIDS-KS?","volume":"95","author":"T.R. Tozetto-Mendoza","year":"2016","journal-title":"Med. (United States)"},{"key":"pone.0274058.ref017","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/ced.13605","article-title":", Evolution of Kaposi sarcoma in the past 30 years in a tertiary hospital of the European Mediterranean basin, Clin","volume":"44","author":"J. Marcoval","year":"2019","journal-title":"Exp. Dermatol"},{"key":"pone.0274058.ref018","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.virol.2009.12.005","article-title":"Human herpesvirus type 8 variants circulating in Europe, Africa and North America in classic, endemic and epidemic Kaposi\u2019s sarcoma lesions during pre-AIDS and AIDS era","volume":"398","author":"M.L. Tornesello","year":"2010","journal-title":"Virology"},{"key":"pone.0274058.ref019","doi-asserted-by":"crossref","first-page":"197828","DOI":"10.1016\/j.virusres.2019.197828","article-title":"Introduction of human gammaherpesvirus 8 genotypes A, B, and C into Brazil from multiple geographic regions","volume":"276","author":"A. de Oliveira Lopes","year":"2020","journal-title":"Virus Res"},{"key":"pone.0274058.ref020","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1002\/jmv.24876","article-title":"Diversity of human herpesvirus 8 genotypes in patients with AIDS and non-AIDS associated Kaposi\u2019s sarcoma, Castleman\u2019s disease and primary effusion lymphoma in Argentina","volume":"89","author":"C.L. P\u00e9rez","year":"2017","journal-title":"J. Med. Virol"},{"key":"pone.0274058.ref021","first-page":"166","article-title":"Detection and genetic polymorphism of human herpes virus type 8 in endemic or epidemic Kaposi\u2019s sarcoma from west and central Africa, and south America","volume":"85","author":"N. Fouchard","year":"2000","journal-title":"J. Cancer"},{"key":"pone.0274058.ref022","article-title":"Variability and evolution of Kaposi\u201as sarcoma-associated herpesvirus in Europe and Africa","volume":"13","author":"P.M. Cook","year":"1999","journal-title":"AIDS"},{"issue":"1","key":"pone.0274058.ref023","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1006\/viro.1999.9853","article-title":"Individuals from North America, Australasia, and Africa are infected with four different genotypes of human herpesvirus 8","volume":"261","author":"Y. X. Meng","year":"1999","journal-title":"Virology"},{"key":"pone.0274058.ref024","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1002\/jmv.23246","article-title":"In vivo and in vitro evidence for an association between the route-specific transmission of HHV-8 and the virus genotype","volume":"84","author":"B. Matteoli","year":"2012","journal-title":"J. Med. Virol"},{"issue":"2","key":"pone.0274058.ref025","article-title":"Epidemiology and Genetic Variability of HHV-8\/KSHV among Rural Populations and Kaposi\u2019s Sarcoma Patients in Gabon, Central Africa","volume":"13","author":"A.I. Mamimandjiami","year":"2021","journal-title":"Review of the Geographical Distribution of HHV-8 K1 Genotypes in Africa. Viruses"},{"key":"pone.0274058.ref026","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.virol.2012.06.014","article-title":"Kaposi\u2019s Sarcoma and Human Herpesvirus 8 in Cuba: Evidence of subtype B expansion","volume":"432","author":"V. Kour\u00ed","year":"2012","journal-title":"Virology"},{"key":"pone.0274058.ref027","article-title":"Prevalence and Risk Factors of Human Herpes Virus Type 8 (HHV-8), Human Immunodeficiency Virus-1 (HIV-1), and Syphilis among Female Sex Workers in Malindi, Kenya","author":"MM Nzivo","year":"2019","journal-title":"Interdiscip Perspect Infect Dis"},{"key":"pone.0274058.ref028","article-title":"Malaria Is Associated With Kaposi Sarcoma-Associated Herpesvirus Seroconversion in a Cohort of Western Kenyan Children","author":"KR Sabourin","journal-title":"J Infect Dis"},{"key":"pone.0274058.ref029","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12936-019-2863-2","article-title":"Imported cases of malaria in Spain: observational study using nationally reported statistics and surveillance data, 2002\u20132015","volume":"18","author":"Z Herrador","year":"2019","journal-title":"Malar J"},{"key":"pone.0274058.ref030","first-page":"1952","article-title":"Genital herpes","volume":"46","author":"F. Boralevi","year":"1996","journal-title":"Rev. Prat"},{"key":"pone.0274058.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-014-0119-0","article-title":"Analysis of the ORF K1 hypervariable regions reveal distinct HHV-8 clustering in Kaposi\u2019s sarcoma and non-Kaposi\u2019s cases","volume":"34","author":"P. Cordiali-Fei","year":"2015","journal-title":"J. Exp. Clin. Cancer Res"},{"key":"pone.0274058.ref032","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1002\/jmv.21322","article-title":"HHV8 a subtype is associated with rapidly evolving classic Kaposi\u2019s sarcoma","volume":"80","author":"R. Mancuso","year":"2008","journal-title":"J. Med. Virol"},{"key":"pone.0274058.ref033","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1086\/656045","article-title":"Kaposi Sarcoma (KS)-Associated Herpesvirus MicroRNA Sequence Analysis and KS Risk in a European AIDS-KS Case Control Study","volume":"202","author":"V. Marshall","year":"2010","journal-title":"J. Infect. Dis"},{"key":"pone.0274058.ref034","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jcv.2004.09.026","article-title":"Molecular characterization of Kaposi\u2019s sarcoma associated herpesvirus (KSHV) from patients with AIDS-associated Kaposi\u2019s sarcoma in S\u00e3o Paulo, Brazil","volume":"33","author":"M.C. Nascimento","year":"2005","journal-title":"J. Clin. 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