{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:05:33Z","timestamp":1788458733099,"version":"build-2803163510"},"posted":{"date-parts":[[2026,4,8]]},"group-title":"Microbiology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020400","name":"John Black Charitable Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100020400","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04e3zg361","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Varicella-zoster virus (VZV) is the etiological agent of chickenpox and herpes zoster, while herpes simplex virus 1 (HSV-1) causes oral and genital herpes. Both infections manifest with skin blisters from which the viruses are transmitted to new hosts either via aerosol (VZV) or skin microabrasions (HSV-1). VZV reaches the skin through the blood route, and in the skin epidermis it first infects undifferentiated keratinocytes of the basal layer. Conflicting evidence exists for HSV-1, making it unclear whether HSV-1 infects undifferentiated or differentiated keratinocytes. Here, we developed\n                  <jats:italic>in vitro<\/jats:italic>\n                  models of primary human epidermal keratinocytes\u2019 differentiation to recapitulate infection of distinct layers of the epidermis by VZV and HSV-1. Our data show that replication of both viruses is restricted, VZV more than HSV-1, if initial infection occurs in differentiated keratinocytes, but not if initial infection occurs in basal undifferentiated keratinocytes. Like VZV, HSV-1 downregulates expression of proteins associated with keratinocyte differentiation, such as the suprabasal keratin K10. However, whereas in VZV downregulation of K10 occurs soon after VZV infection and appears to be independent from viral replication, HSV-1-mediated K10 downregulation requires full viral replication. These observations provide insights into the potential for VZV and HSV-1 interactions with epidermal differentiation to yield strategies for developing host- and pathogen-directed antiviral agents.\n                <\/jats:p>","DOI":"10.64898\/2026.04.08.717198","type":"posted-content","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:40:12Z","timestamp":1775709612000},"source":"Crossref","is-referenced-by-count":1,"title":["Comparative analysis of varicella-zoster virus and herpes simplex virus 1 interaction with epidermal terminal differentiation in primary human keratinocytes models of differentiation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-5088","authenticated-orcid":false,"given":"Cristina","family":"Tommasi","sequence":"first","affiliation":[{"name":"Infection, Immunity and Inflammation Department, University College London GOS Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geonhee","family":"Kim","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Department, University College London GOS Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Department, University College London GOS Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriani","family":"Drousioti","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Department, University College London GOS Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olumide","family":"Ogunbiyi","sequence":"additional","affiliation":[{"name":"Histopathology Department, Camelia Botnar Laboratories, University College London Great Ormond Street Hospital for Children, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4234-6037","authenticated-orcid":false,"given":"Oscar Enrique Torres","family":"Montaguth","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Department, University College London GOS Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Mosahebi","sequence":"additional","affiliation":[{"name":"Department of Surgical Biotechnology, Royal Free Hospital, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-0534","authenticated-orcid":false,"given":"Judith","family":"Breuer","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Department, University College London GOS Institute of Child Health, London, 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