{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:42:37Z","timestamp":1791808957043,"version":"4.3.4"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"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":["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":"\nIntroduction<\/jats:title>\nMeningoencephalitis in children poses a diagnostic challenge, as etiology remains unknown for most of patients. Viral metagenomics by shotgun sequencing represents a powerful tool for investigating unknown viral infections related to these cases.<\/jats:p>\n<\/jats:sec>\n\nPatients and methods<\/jats:title>\nIn a two-year, reference-centre, retrospective study, we investigated the usefulness of viral metagenomics of cerebrospinal fluid (CSF) for the diagnosis of viral infectious meningoencephalitis in forty seven pediatric patients, forty of them previously tested negative with a routine neurologic panel of viral targets that included herpesvirus 1\u20133 and enterovirus. We enhanced the detection by targeting viral sequences by hybrid capture. Raw sequence data was analysed using three bioinformatics pipelines.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nOut of forty remaining children with meningoencephalitis of unknown viral etiology, a significant detection of viral nucleic acid by shotgun sequencing was found in twenty one, which was confirmed in ten of them by specific PCR: seven human endogenous retrovirus K113 (HER K113), one parechovirus 3, one human herpesvirus 5 (HHV5); one enterovirus B (Echovirus 9). The remaining eleven CSF were not confirmed by PCR: three rotavirus, one human herpesvirus 7 (HHV7), one influenza A, one mastadenovirus C, one sindbis virus, one torque teno virus, one human immunodeficiency virus 1 (HIV-1), one human alphaherpesvirus 3 (HHV3), one human alphaherpesvirus 2 (HHV2).<\/jats:p>\n<\/jats:sec>\n\nConclusions<\/jats:title>\nUnderutilization of currently available meningitis-encephalitis diagnostic techniques such as BioFire\u00ae FilmArray\u00ae is the main cause of undiagnosed cases of meningoencephalitis. However, in this study we detected uncommon viruses that should be considered, including virus, rotavirus, sindbis virus, influenza A virus and HHV7. No other viral sequences that could be readily linked to CNS inflammation were detected. Some findings may stem from reagent or sample contamination, as seen with papillomavirus; for others, the clinical relevance of the virus remains uncertain and should be substantiated by further studies, as is the case with endogenous retrovirus K113 virus. Online bioinformatics pipeline CZID represents a valuable tool for analysing shotgun sequencing data in cases of neurological conditions with unknown etiology. Altogether, this study highlights the potential of shotgun sequencing in identifying previously unknown viral neuropathogens and sheds light on the interpretation issues related to its application in clinical microbiology.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0296036","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T18:51:35Z","timestamp":1703184695000},"page":"e0296036","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Shotgun metagenomics to investigate unknown viral etiologies of pediatric meningoencephalitis"],"prefix":"10.1371","volume":"18","author":[{"given":"Andrea","family":"Castellot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Camacho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Fern\u00e1ndez-Garc\u00eda","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":[[2023,12,21]]},"reference":[{"key":"pone.0296036.ref001","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"Global, regional, and national burden of neurological disorders, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"GBD 2016 Neurology Collaborators","year":"2019","journal-title":"Lancet Neurol"},{"key":"pone.0296036.ref002","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S1473-3099(10)70222-X","article-title":"Causes of encephalitis and differences in their clinical presentations in England: A multicentre, population-based prospective study","volume":"10","author":"J. 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