{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:18:56Z","timestamp":1790126336366,"version":"4.0.1"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005073","name":"Agency for Defense Development","doi-asserted-by":"publisher","award":["UE202026GD"],"award-info":[{"award-number":["UE202026GD"]}],"id":[{"id":"10.13039\/501100005073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-2017M3A9E4061992"],"award-info":[{"award-number":["NRF-2017M3A9E4061992"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Hantavirus infection occurs through the inhalation of aerosolized excreta, including urine, feces, and saliva of infected rodents. The presence of Hantaan virus (HTNV) RNA or infectious particles in urine specimens of patient with hemorrhagic fever with renal syndrome (HFRS) remains to be investigated.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/Principal findings<\/jats:title>\n<jats:p>We collected four urine and serum specimens of Republic of Korea Army (ROKA) patients with HFRS. We performed multiplex PCR-based next-generation sequencing (NGS) to obtain the genome sequences of clinical HTNV in urine specimens containing ultra-low amounts of viral genomes. The epidemiological and phylogenetic analyses of HTNV demonstrated geographically homogenous clustering with those in <jats:italic>Apodemus agrarius<\/jats:italic> captured in highly endemic areas, indicating that phylogeographic tracing of HTNV genomes reveals the potential infection sites of patients with HFRS. Genetic exchange analyses showed a genetic configuration compatible with HTNV L segment exchange in nature.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusion\/Significance<\/jats:title>\n<jats:p>Our results suggest that whole or partial genome sequences of HTNV from the urine enabled to track the putative infection sites of patients with HFRS by phylogeographically linking to the zoonotic HTNV from the reservoir host captured at endemic regions. This report raises awareness among physicians for the presence of HTNV in the urine of patients with HFRS.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0009707","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T20:02:44Z","timestamp":1632859364000},"page":"e0009707","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Urinary genome detection and tracking of Hantaan virus from hemorrhagic fever with renal syndrome patients using multiplex PCR-based next-generation sequencing"],"prefix":"10.1371","volume":"15","author":[{"given":"Seungchan","family":"Cho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3178-8569","authenticated-orcid":true,"given":"Won-Keun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Sun","family":"No","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehun","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8553-7189","authenticated-orcid":true,"given":"Yongjin","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayne Cho","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geum-Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungmin","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Ah","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongwoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daesang","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Hun","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Tae","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-8332","authenticated-orcid":true,"given":"Jin-Won","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"issue":"8","key":"pntd.0009707.ref001","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nrmicro3066","article-title":"Uncovering the mysteries of hantavirus infections","volume":"11","author":"A Vaheri","year":"2013","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"pntd.0009707.ref002","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1128\/CMR.00062-09","article-title":"A global perspective on hantavirus ecology, epidemiology, and disease","volume":"23","author":"CB Jonsson","year":"2010","journal-title":"Clin Microbiol Rev"},{"issue":"6","key":"pntd.0009707.ref003","first-page":"1030","article-title":"Hantavirus regulation of endothelial cell functions","volume":"102","author":"ER Mackow","year":"2009","journal-title":"Thromb Haemost"},{"issue":"2","key":"pntd.0009707.ref004","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3201\/eid0302.970202","article-title":"Hantaviruses: a global disease problem","volume":"3","author":"C Schmaljohn","year":"1997","journal-title":"Emerg Infect Dis"},{"issue":"9","key":"pntd.0009707.ref005","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1093\/infdis\/jis475","article-title":"Hantaan virus RNA load in patients having hemorrhagic fever with renal syndrome: correlation with disease severity","volume":"207","author":"J Yi","year":"2013","journal-title":"J Infect Dis"},{"issue":"1","key":"pntd.0009707.ref006","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1080\/22221751.2020.1760144","article-title":"Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient","volume":"9","author":"J Sun","year":"2020","journal-title":"Emerg Microbes Infect"},{"issue":"1","key":"pntd.0009707.ref007","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3201\/eid2101.140894","article-title":"Detection of Zika virus in urine","volume":"21","author":"AC Gourinat","year":"2015","journal-title":"Emerg Infect Dis"},{"issue":"7","key":"pntd.0009707.ref008","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1093\/infdis\/jit290","article-title":"Excretion of West Nile virus in urine during acute infection","volume":"208","author":"L Barzon","year":"2013","journal-title":"J Infect Dis"},{"issue":"3","key":"pntd.0009707.ref009","doi-asserted-by":"crossref","first-page":"406","DOI":"10.3201\/eid1403.071242","article-title":"Hantavirus RNA in saliva from patients with hemorrhagic fever with renal syndrome","volume":"14","author":"L Pettersson","year":"2008","journal-title":"Emerg Infect Dis"},{"issue":"10","key":"pntd.0009707.ref010","doi-asserted-by":"crossref","first-page":"5046","DOI":"10.1128\/JVI.02409-08","article-title":"Andes virus antigens are shed in urine of patients with acute hantavirus cardiopulmonary syndrome","volume":"83","author":"P Godoy","year":"2009","journal-title":"J Virol"},{"issue":"8","key":"pntd.0009707.ref011","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nrmicro2614","article-title":"Why do RNA viruses recombine?","volume":"9","author":"E Simon-Loriere","year":"2011","journal-title":"Nat Rev Microbiol"},{"issue":"Pt 8","key":"pntd.0009707.ref012","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1099\/vir.0.011304-0","article-title":"Analysis of Puumala hantavirus in a bank vole population in northern Finland: evidence for co-circulation of two genetic lineages and frequent reassortment between strains","volume":"90","author":"M Razzauti","year":"2009","journal-title":"J Gen Virol"},{"issue":"2","key":"pntd.0009707.ref013","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1006\/viro.1995.0071","article-title":"Naturally occurring Sin Nombre virus genetic reassortants","volume":"214","author":"WW Henderson","year":"1995","journal-title":"Virology"},{"issue":"8","key":"pntd.0009707.ref014","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1128\/JCM.38.8.3029-3035.2000","article-title":"Genetic diversity, distribution, and serological features of hantavirus infection in five countries in South America","volume":"38","author":"PJ Padula","year":"2000","journal-title":"J Clin Microbiol"},{"key":"pntd.0009707.ref015","doi-asserted-by":"crossref","first-page":"44369","DOI":"10.1038\/srep44369","article-title":"Dynamic Circulation and Genetic Exchange of a Shrew-borne Hantavirus, Imjin virus, in the Republic of Korea","volume":"7","author":"SH Lee","year":"2017","journal-title":"Sci Rep."},{"issue":"6","key":"pntd.0009707.ref016","doi-asserted-by":"crossref","first-page":"e0004650","DOI":"10.1371\/journal.pntd.0004650","article-title":"Genetic Diversity and Reassortment of Hantaan Virus Tripartite RNA Genomes in Nature, the Republic of Korea","volume":"10","author":"JA Kim","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0009707.ref017","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/cid\/ciz234","article-title":"Active Targeted Surveillance to Identify Sites of Emergence of Hantavirus","volume":"70","author":"WK Kim","year":"2020","journal-title":"Clin Infect Dis"},{"issue":"4","key":"pntd.0009707.ref018","first-page":"840","article-title":"Evaluation of urine as a clinical specimen for diagnosis of hepatitis A","volume":"9","author":"MS Joshi","year":"2002","journal-title":"Clin Diagn Lab Immunol"},{"issue":"4","key":"pntd.0009707.ref019","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1093\/cid\/cir804","article-title":"Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and correlates of fatal outcome","volume":"54","author":"YZ Zhang","year":"2012","journal-title":"Clin Infect Dis"},{"issue":"9","key":"pntd.0009707.ref020","doi-asserted-by":"crossref","first-page":"e0004100","DOI":"10.1371\/journal.pntd.0004100","article-title":"Value of Routine Dengue Diagnostic Tests in Urine and Saliva Specimens","volume":"9","author":"AC Andries","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"pntd.0009707.ref021","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.3346\/jkms.2020.35.e86","article-title":"Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea","volume":"35","author":"JY Kim","year":"2020","journal-title":"J Korean Med Sci"},{"issue":"11","key":"pntd.0009707.ref022","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1086\/516786","article-title":"Prospective evaluation of household contacts of persons with hantavirus cardiopulmonary syndrome in chile","volume":"195","author":"M Ferres","year":"2007","journal-title":"J Infect Dis"},{"issue":"2","key":"pntd.0009707.ref023","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3201\/eid0302.970210","article-title":"An unusual hantavirus outbreak in southern Argentina: person-to-person transmission? Hantavirus Pulmonary Syndrome Study Group for Patagonia","volume":"3","author":"RM Wells","year":"1997","journal-title":"Emerg Infect Dis"},{"issue":"8","key":"pntd.0009707.ref024","article-title":"Shedding and Transmission Modes of Severe Fever With Thrombocytopenia Syndrome Phlebovirus in a Ferret Model","volume":"6","author":"KM Yu","year":"2019","journal-title":"Open Forum Infect Dis"},{"issue":"1","key":"pntd.0009707.ref025","first-page":"9","article-title":"CK. S, Seong I, Kim J. Korean Hemorrhagic Fever VII. Transmission of Hantaan virus, the Etologic Agent of Korean Hemorrhagic Fever, in Apodemus agrarius","volume":"12","author":"H Lee","year":"1982","journal-title":"J Bacteriol Virol"},{"issue":"2","key":"pntd.0009707.ref026","first-page":"181","article-title":"Demonstration of Hantaan Virus Antigens in Cells in Urine Sediments from Hemorrhageic Fever with Renal Syndrome Patients","volume":"22","author":"I. Seong","year":"1992","journal-title":"J Bacteriol Virol"},{"issue":"4","key":"pntd.0009707.ref027","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3346\/jkms.1998.13.4.389","article-title":"Metabolic acidosis and urinary acidification defect during the course of hemorrhagic fever with renal syndrome","volume":"13","author":"JS Han","year":"1998","journal-title":"J Korean Med Sci"},{"issue":"3","key":"pntd.0009707.ref028","doi-asserted-by":"crossref","first-page":"48","DOI":"10.32607\/20758251-2015-7-3-48-54","article-title":"Extracellular Nucleic Acids in Urine: Sources, Structure, Diagnostic Potential","volume":"7","author":"OE Bryzgunova","year":"2015","journal-title":"Acta Naturae"},{"key":"pntd.0009707.ref029","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jviromet.2017.04.018","article-title":"Stability of Zika virus in urine: Specimen processing considerations and implications for the detection of RNA targets in urine","volume":"248","author":"SK Tan","year":"2017","journal-title":"J Virol Methods"},{"issue":"6","key":"pntd.0009707.ref030","doi-asserted-by":"crossref","first-page":"537","DOI":"10.2353\/jmoldx.2009.080164","article-title":"Evaluation of pre-analytical variables in the quantification of dengue virus by real-time polymerase chain reaction","volume":"11","author":"A Anwar","year":"2009","journal-title":"J Mol Diagn"},{"issue":"1\u20132","key":"pntd.0009707.ref031","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jviromet.2008.02.003","article-title":"Viral nucleic acid stabilization by RNA extraction reagent","volume":"150","author":"JA Blow","year":"2008","journal-title":"J Virol Methods"},{"issue":"3","key":"pntd.0009707.ref032","doi-asserted-by":"crossref","first-page":"ofz048","DOI":"10.1093\/ofid\/ofz048","article-title":"Viral RNA Degradation Makes Urine a Challenging Specimen for Detection of Japanese Encephalitis Virus in Patients with Suspected CNS Infection","volume":"6","author":"T Bharucha","year":"2019","journal-title":"Open Forum Infect Dis"},{"issue":"1","key":"pntd.0009707.ref033","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1006\/viro.1997.8990","article-title":"Genetic reassortment among viruses causing hantavirus pulmonary syndrome","volume":"242","author":"LL Rodriguez","year":"1998","journal-title":"Virology"},{"issue":"1\u20132","key":"pntd.0009707.ref034","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.virol.2013.07.030","article-title":"Viruses of the family Bunyaviridae: are all available isolates reassortants?","volume":"446","author":"T Briese","year":"2013","journal-title":"Virology"},{"key":"pntd.0009707.ref035","doi-asserted-by":"crossref","first-page":"26017","DOI":"10.1038\/srep26017","article-title":"Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing","volume":"6","author":"WK Kim","year":"2016","journal-title":"Sci Rep"},{"issue":"7","key":"pntd.0009707.ref036","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular evolutionary genetics analysis version 7.0","volume":"33","author":"S Kumar","year":"2015","journal-title":"Mol Biol Evol"},{"issue":"8","key":"pntd.0009707.ref037","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1093\/bioinformatics\/17.8.754","article-title":"MRBAYES: Bayesian inference of phylogenetic trees","volume":"17","author":"JP Huelsenbeck","year":"2001","journal-title":"Bioinformatics"},{"issue":"5","key":"pntd.0009707.ref038","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1128\/JVI.02163-13","article-title":"Genomewide analysis of reassortment and evolution of human influenza A(H3N2) viruses circulating between 1968 and 2011","volume":"88","author":"KB Westgeest","year":"2014","journal-title":"J Virol"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T20:03:39Z","timestamp":1632859419000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009707"}},"subtitle":[],"editor":[{"given":"Michael R.","family":"Holbrook","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0009707","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,28]]}}}