{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:05:32Z","timestamp":1791443132408,"version":"4.3.3"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Institute of Allergy and Infectious Diseases","award":["R01AI125111"],"award-info":[{"award-number":["R01AI125111"]}]},{"name":"The National Institute of Allergy and Infectious Diseases","award":["R01AI178128"],"award-info":[{"award-number":["R01AI178128"]}]},{"name":"The National Institute of Allergy and Infectious Diseases","award":["R21AR082631"],"award-info":[{"award-number":["R21AR082631"]}]},{"DOI":"10.13039\/100000069","name":"The National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AI125111"],"award-info":[{"award-number":["R01AI125111"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"The National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AI178128"],"award-info":[{"award-number":["R01AI178128"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"The National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R21AR082631"],"award-info":[{"award-number":["R21AR082631"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Herpes simplex virus-1 (HSV-1) is common and can cause significant disease in humans. Unfortunately, efforts to develop effective vaccines against HSV-1 have so far failed. A detailed understanding of how the virus infects its host and how the host mounts potent immune responses against the virus may inform new vaccine approaches. Here, using a zosteriform mouse model, we examined how the HSV-1 gene UL56 affects the ability of the virus to cause morbidity and generate protective immunity. A UL56 deletion mutant, \u0394UL56, was derived from the wild-type HSV-1 strain SC16, alongside a revertant strain in which UL56 was reintroduced in \u0394UL56. In vitro, the three virus strains replicated in a similar manner; however, in vivo, only the wild type and the revertant strains caused shingles-like skin lesions and death. Mice previously infected with \u0394UL56 became resistant to a lethal challenge with the wild-type SC16. The protective immunity induced by \u0394UL56 was independent of IL-1, IL-33, and IL-36 signaling through IL-1RAP. Both skin and intramuscular \u0394UL56 inoculation generated protective immunity against a lethal SC16 challenge. After 6 months, female mice remained resistant to infection, while male mice exhibited signs of declining protection. Our data demonstrate that UL56 is important for the ability of HSV-1 to spread within the infected host and that a \u2206UL56 strain elicits an effective immune response against HSV-1 despite this loss of virulence. These findings may guide further HSV-1 vaccine development.<\/jats:p>","DOI":"10.3390\/vaccines12080837","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T06:11:36Z","timestamp":1721887896000},"page":"837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["UL56 Is Essential for Herpes Simplex Virus-1 Virulence In Vivo but Is Dispensable for Induction of Host-Protective Immunity"],"prefix":"10.3390","volume":"12","author":[{"given":"Nopprarat","family":"Tongmuang","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Inflammation, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Center for Inflammation and Lung Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Inflammation, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Center for Inflammation and Lung Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viv","family":"Connor","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9918-9998","authenticated-orcid":false,"given":"Colin","family":"Crump","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liselotte E.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Inflammation, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Center for Inflammation and Lung Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Cancer Signaling and Microenvironment, Fox Chase Cancer Center, Temple Health, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108235","DOI":"10.1016\/j.celrep.2020.108235","article-title":"Temporal Proteomic Analysis of Herpes Simplex Virus 1 Infection Reveals Cell-Surface Remodeling via pUL56-Mediated GOPC Degradation","volume":"33","author":"Soh","year":"2020","journal-title":"Cell Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100014","DOI":"10.1016\/j.cellin.2022.100014","article-title":"Herpes simplex virus protein UL56 inhibits cGAS-Mediated DNA sensing to evade antiviral immunity","volume":"1","author":"Zheng","year":"2022","journal-title":"Cell Insight"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114122","DOI":"10.1016\/j.celrep.2024.114122","article-title":"HSV-1 employs UL56 to antagonize expression and function of cGAMP channels","volume":"43","author":"Blest","year":"2024","journal-title":"Cell Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1038\/s41598-018-22682-2","article-title":"Herpesviruses possess conserved proteins for interaction with Nedd4 family ubiquitin E3 ligases","volume":"8","author":"Koshizuka","year":"2018","journal-title":"Sci. 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