{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:41Z","timestamp":1785437021630,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Disease Prevention and Control (CCM) of the Italian Ministry of Health"},{"DOI":"10.13039\/501100000780","name":"EU","doi-asserted-by":"publisher","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Herpes simplex virus 1 (HSV-1) is a rare cause of acute hepatitis, especially in patients with chronic immunosuppression. We performed whole-genome HSV-1 sequencing with a metagenomics approach on peripheral blood samples from an Italian case of fatal acute liver failure with high circulating HSV-1 (1,129,900,000 copies\/mL), followed by phylogenetic analysis. After multiple sequence alignment, a final dataset of 182 whole-genome sequences was selected. The sequenced HSV-1 strain belonged to a phylogenetic clade isolated in Florida in 2002 (OQ724868.1). A characterization of single nucleotide polymorphisms and indels was performed to determine their effects on the viral genome: only one variant, classified as an indel, was detected with a high impact effect (c.905_906insGTTTT) in the UL49A gene, which is known to encode a membrane protein regulating virion morphogenesis, replication and assembly. In addition, this study also detected variants in other genes involved in crucial steps of the HSV-1 life cycle, like alpha-regulation (US7), capsid transport (UL36) and viral polymerase function (UL30). In conclusion, the results of this variant analysis confirmed that in HSV-1 hepatitis, some viral regions may be hotspots for adaptive mutations with a substantial impact on viral replication or immune evasion.<\/jats:p>","DOI":"10.3390\/ijms27135640","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phylogenetic and Genomic Characterization of Whole Genome Sequences of a Herpes Simplex Virus Type 1 Isolate Identified Genomic Variant Characteristics in a Human Subject with Fulminant Hepatitis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3338-5416","authenticated-orcid":false,"given":"Carlo","family":"Smirne","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"},{"name":"Internal Medicine Unit, San Giovanni Bosco Hospital, ASL Citt\u00e0 di Torino, 10154 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Romano","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ravanini","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Crobu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"},{"name":"Clinical Biochemistry Laboratory, Department of Laboratory Medicine, City of Health and Science University Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1478-6094","authenticated-orcid":false,"given":"Guglielmo","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Mercandino","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Maggiore della Carit\u00e0 Hospital, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-259X","authenticated-orcid":false,"given":"Elena","family":"Grossini","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9740-0155","authenticated-orcid":false,"given":"Mario","family":"Pirisi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6062-2579","authenticated-orcid":false,"given":"Antonio","family":"Piralla","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1002\/lt.21250","article-title":"Herpes Simplex Virus Hepatitis: An Analysis of the Published Literature and Institutional Cases","volume":"13","author":"Norvell","year":"2007","journal-title":"Liver Transpl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1111\/liv.15215","article-title":"Comprehensive Clinical and Virological Characterization of Three Cases of Fulminant Liver Failure Owing to HSV1 Primary Infection","volume":"42","author":"Spahn","year":"2022","journal-title":"Liver Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e01485","DOI":"10.1016\/j.idcr.2022.e01485","article-title":"Primary Herpes Simplex Virus Type 1 Infection with Acute Liver Failure in Solid Organ Transplantation: Report of Three Cases and Review","volume":"28","author":"Arana","year":"2022","journal-title":"IDCases"},{"key":"ref_4","first-page":"107","article-title":"Fulminant Hepatitis Following Primary Herpes Simplex Virus Infection","volume":"22","author":"Pinney","year":"2011","journal-title":"Saudi J. 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