{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:20:16Z","timestamp":1772252416938,"version":"3.50.1"},"reference-count":20,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2023YFA1801900"],"award-info":[{"award-number":["2023YFA1801900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["L246002"],"award-info":[{"award-number":["L246002"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["11100704"],"award-info":[{"award-number":["11100704"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["2023YFA1801900"],"award-info":[{"award-number":["2023YFA1801900"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["L246002"],"award-info":[{"award-number":["L246002"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["11100704"],"award-info":[{"award-number":["11100704"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002726","name":"Beijing Normal University","doi-asserted-by":"publisher","award":["2023YFA1801900"],"award-info":[{"award-number":["2023YFA1801900"]}],"id":[{"id":"10.13039\/501100002726","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002726","name":"Beijing Normal University","doi-asserted-by":"publisher","award":["L246002"],"award-info":[{"award-number":["L246002"]}],"id":[{"id":"10.13039\/501100002726","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002726","name":"Beijing Normal University","doi-asserted-by":"publisher","award":["11100704"],"award-info":[{"award-number":["11100704"]}],"id":[{"id":"10.13039\/501100002726","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Background: To provide clues and a diagnostic basis for patients with fever of unknown origin through urinary proteomics analysis. Methods: For the first time, an attempt was made to conduct a full-library search for viruses in urine samples. Liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) technology was employed to analyze the urinary proteomes of patients with fever of unknown origin, and to search for and identify viral protein fragments. In this study, there is no need to pre-determine the types of substances present in the samples. As long as the relevant sequences of viruses are available in the database, virus searches can be performed on the samples. Results: In the urine samples, multiple specific peptides from various viruses, such as the monkeypox virus, salivirus A, human herpesvirus 8 type P, Middle East respiratory syndrome-related coronavirus, rotavirus A, Orf virus (strain NZ2), human herpesvirus 2 (strain HG52), human adenovirus E serotype 4, influenza A virus, human coronavirus NL63, parainfluenza virus 5 (strain W3), Nipah virus, and hepatitis C virus genotype 2k (isolate VAT96), could be observed. It was found that the detection amounts of multiple viruses in febrile patients were much higher than those in the control group. Among them, the increase multiple of salivirus A was as high as more than 4200 times, and the increase multiples of multiple viral proteins were higher than 20 times. Conclusions: Viral fragments in urinary proteins can be reliably identified using mass spectrometry, which provides clues for the investigation of unexplained fever and may also be applied to the exploration of any unknown diseases.<\/jats:p>","DOI":"10.3390\/biology14040318","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T04:58:38Z","timestamp":1742533118000},"page":"318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Viral Fragments in the Urine Proteome: New Clues to the Cause of Fever"],"prefix":"10.3390","volume":"14","author":[{"given":"Minhui","family":"Yang","sequence":"first","affiliation":[{"name":"Gene Engineering Drug and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0853-9682","authenticated-orcid":false,"given":"Yan","family":"Su","sequence":"additional","affiliation":[{"name":"Gene Engineering Drug and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Gene Engineering Drug and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-2558","authenticated-orcid":false,"given":"Youhe","family":"Gao","sequence":"additional","affiliation":[{"name":"Gene Engineering Drug and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1007\/s00508-016-1083-9","article-title":"Fever of unknown origin (FUO) revised","volume":"128","author":"Unger","year":"2016","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"280","DOI":"10.7861\/clinmedicine.15-3-280","article-title":"Fever of unknown origin","volume":"15","author":"Simon","year":"2015","journal-title":"Clin. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"690","DOI":"10.21037\/atm-20-3875","article-title":"Retrospective analysis of 1641 cases of classic fever of unknown origin","volume":"8","author":"Zhou","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1002\/prca.200900008","article-title":"Urine proteomics for profiling of human disease using high accuracy mass spectrometry","volume":"3","author":"Kentsis","year":"2009","journal-title":"Proteom. Clin. Appl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s11427-019-9562-y","article-title":"Now is the time to test early urinary biomarkers in large\u2014Scale human samples","volume":"62","author":"Gao","year":"2019","journal-title":"Sci. China Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/14789450.2021.1937133","article-title":"Early disease biomarkers can be found using animal models urine proteomics","volume":"18","author":"Wei","year":"2021","journal-title":"Expert Rev. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.urine.2023.06.001","article-title":"Urine; a new promising biological fluid to act as a non-invasive biomarker for different human diseases","volume":"5","author":"Balhara","year":"2023","journal-title":"URINE"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1182\/blood.V28.3.465.465","article-title":"Virus-like particles and cytopathic activity in urine of patients with leukemia","volume":"28","author":"Ames","year":"1966","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cvjetkovic, I.H., Radovanov, J., Kovacevic, G., Turkulov, V., and Pati\u0107, A. (2023). Diagnostic value of urine qRT-PCR for the diagnosis of West Nile virus neuroinvasive disease. Diagn. Microbiol. Infect. Dis., 107.","DOI":"10.1016\/j.diagmicrobio.2023.115920"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1021\/acs.jproteome.1c00391","article-title":"Mass Spectrometric Analysis of Urine from COVID-19 Patients for Detection of SARS-CoV-2 Viral Antigen and to Study Host Response","volume":"20","author":"Chavan","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Niedrig, M., Patel, P., El Wahed, A.A., Sch\u00e4dler, R., and Yactayo, S. (2018). Find the right sample: A study on the versatility of saliva and urine samples for the diagnosis of emerging viruses. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3611-x"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4103\/ijmr.IJMR_808_18","article-title":"Urinary immunoglobulins in viral diagnosis: An overview","volume":"155","author":"Mohandas","year":"2022","journal-title":"Indian. J. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-Spectrometric exploration of proteome structure and function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1590\/1806-9282.65.8.1109","article-title":"Fever of unknown origin\u2014A literature review","volume":"65","author":"Santana","year":"2019","journal-title":"Rev. Assoc. Med. Bras. (1992)"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nature05762","article-title":"Herpesvirus latency confers symbiotic protection from bacterial infection","volume":"447","author":"Barton","year":"2007","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1600-065X.2011.01074.x","article-title":"Immune modulation during latent herpesvirus infection","volume":"245","author":"White","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.coviro.2021.10.001","article-title":"Progress and prospects of the healthy human gut virome","volume":"51","author":"Stockdale","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"O111.016717","DOI":"10.1074\/mcp.O111.016717","article-title":"Targeted data extraction of the MS\/MS spectra generated by data\u2014Independent acquisition: A new concept for consistent and accurate proteome analysis","volume":"11","author":"Gillet","year":"2012","journal-title":"Mol. Cell Proteom."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Patowary, A., Chauhan, R.K., Singh, M., Kv, S., Periwal, V., Kp, K., Sapkal, G.N., Bondre, V.P., Gore, M.M., and Sivasubbu, S. (2012). De novo identification of viral pathogens from cell culture hologenomes. BMC Res. Notes, 5.","DOI":"10.1186\/1756-0500-5-11"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e01678-18","DOI":"10.1128\/JCM.01678-18","article-title":"Direct identification of pathogens in urine by use of a specific matrix\u2014Assisted laser desorption ionization\u2013time of flight spectrum database","volume":"57","author":"Pinault","year":"2019","journal-title":"J. Clin. Microbiol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/4\/318\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:57:36Z","timestamp":1760029056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/4\/318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":20,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["biology14040318"],"URL":"https:\/\/doi.org\/10.3390\/biology14040318","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.09.19.613984","asserted-by":"object"}]},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]}}}