{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:57:07Z","timestamp":1790906227690,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201700030I"],"award-info":[{"award-number":["HHSN272201700030I"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI122640"],"award-info":[{"award-number":["AI122640"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS064022"],"award-info":[{"award-number":["NS064022"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30 EY08098"],"award-info":[{"award-number":["P30 EY08098"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted Support"],"award-info":[{"award-number":["Unrestricted Support"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Eye &amp; Ear Foundation of Pittsburgh","award":["Unrestricted Support"],"award-info":[{"award-number":["Unrestricted Support"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>There is a continued need to understand varicella-zoster virus (VZV) pathogenesis and to develop more effective antivirals, as it causes chickenpox and zoster. As a human-restricted alphaherpesvirus, the use of human skin in culture and mice is critical in order to reveal the important VZV genes that are required for pathogenesis but that are not necessarily observed in the cell culture. We previously used VZV-expressing firefly luciferase (fLuc), under the control of the constitutively active SV40 promoter (VZV-BAC-Luc), to measure the VZV spread in the same sample. However, the fLuc expression was independent of viral gene expression and viral DNA replication programs. Here, we developed robust reporter VZV viruses by using bacterial artificial chromosome (BAC) technology, expressing luciferase from VZV-specific promoters. We also identified two spurious mutations in VZV-BAC that were corrected for maximum pathogenesis. VZV with fLuc driven by ORF57 showed superior growth in cells, human skin explants, and skin xenografts in mice. The ORF57-driven luciferase activity had a short half-life in the presence of foscarnet. This background was then used to investigate the roles for ORF36 (thymidine kinase (TK)) and ORF13 (thymidylate synthase (TS)) in skin. The studies reveal that VZV-\u2206TS had increased sensitivity to brivudine and was highly impaired for skin replication. This is the first report of a phenotype that is associated with the loss of TS.<\/jats:p>","DOI":"10.3390\/v14040826","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:22:43Z","timestamp":1650414163000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Development of Robust Varicella Zoster Virus Luciferase Reporter Viruses for In Vivo Monitoring of Virus Growth and Its Antiviral Inhibition in Culture, Skin, and Humanized Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Megan G.","family":"Lloyd","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S.","family":"Flot","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2032-5323","authenticated-orcid":false,"given":"Brittany W.","family":"Geiler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1901-9970","authenticated-orcid":false,"given":"Paul R.","family":"Kinchington","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4371-8608","authenticated-orcid":false,"given":"Jennifer F.","family":"Moffat","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"902","DOI":"10.15585\/mmwr.mm6534a4","article-title":"Epidemiology of Varicella During the 2-Dose Varicella Vaccination Program\u2014United States, 2005\u20132014","volume":"65","author":"Lopez","year":"2016","journal-title":"MMWR. 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