{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:17:58Z","timestamp":1788887878171,"version":"build-2803163510"},"reference-count":129,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Human herpesvirus 6 (HHV-6) is a \u03b2-herpesvirus that is highly prevalent in the human population. HHV-6 comprises two recognized species (HHV-6A and HHV-6B). Despite different cell tropism and disease association, HHV-6A\/B show high genome homology and harbor the conserved U94 gene, which is limited to HHV-6 and absent in all the other human herpesviruses. U94 has key functions in the virus life cycle and associated diseases, having demonstrated or putative roles in virus replication, integration, and reactivation. During natural infection, U94 elicits an immune response, and the prevalence and extent of the anti-U94 response are associated with specific diseases. Notably, U94 can entirely reproduce some virus effects at the cell level, including inhibition of cell migration, induction of cytokines and HLA-G expression, and angiogenesis inhibition, supporting a direct U94 role in the development of HHV-6-associated diseases. Moreover, specific U94 properties, such as the ability to modulate angiogenesis pathways, have been exploited to counteract cancer development. Here, we review the information available on this key HHV-6 gene, highlighting its potential uses.<\/jats:p>","DOI":"10.3390\/cells9122608","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T21:37:42Z","timestamp":1607377062000},"page":"2608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The U94 Gene of Human Herpesvirus 6: A Narrative Review of Its Role and Potential Functions"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6048-9141","authenticated-orcid":false,"given":"Elisabetta","family":"Caselli","sequence":"first","affiliation":[{"name":"Section of Microbiology, Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1937-5534","authenticated-orcid":false,"given":"Maria","family":"D\u2019Accolti","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Caccuri","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5274-295X","authenticated-orcid":false,"given":"Irene","family":"Soffritti","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Gentili","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-9561","authenticated-orcid":false,"given":"Daria","family":"Bortolotti","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Rotola","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo","family":"Cassai","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1866-314X","authenticated-orcid":false,"given":"Simona","family":"Fiorentini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9066-7973","authenticated-orcid":false,"given":"Alberto","family":"Zani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Di Luca","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1126\/science.2876520","article-title":"Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders","volume":"234","author":"Salahuddin","year":"1986","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0140-6736(88)91893-4","article-title":"Identification of Human Herpesvirus-6 as a Causal Agent for Exanthem Subitum","volume":"331","author":"Yamanishi","year":"1988","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00705-013-1902-5","article-title":"Classification of HHV-6A and HHV-6B as distinct viruses","volume":"159","author":"Ablashi","year":"2014","journal-title":"Arch. 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