Herpes simplex virus spreads rapidly in human foreskin, partly driven by chemokine-induced redistribution of Nectin-1 on keratinocytes.

Autor: Rana H; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Truong NR; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Johnson B; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Baharlou H; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Herbert JJ; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Kandasamy S; Research and Development, Vaxxas Pty Ltd., Brisbane, Queensland, Australia., Goddard R; Research and Development, Vaxxas Pty Ltd., Brisbane, Queensland, Australia., Cohen RC; University of Sydney and Australian National University, Children's Hospital at Westmead, New South Wales, Australia., Wines M; Urology, Sydney Adventist Hospital, Wahroonga, New South Wales, Australia., Nasr N; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Harman AN; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Bertram KM; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Sandgren KJ; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Cunningham AL; The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Jun 10; Vol. 20 (6), pp. e1012267. Date of Electronic Publication: 2024 Jun 10 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012267
Abstrakt: HSV infects keratinocytes in the epidermis of skin via nectin-1. We established a human foreskin explant infection model to investigate HSV entry and spread. HSV1 entry could only be achieved by the topical application of virus via high density microarray projections (HD-MAPs) to the epidermis, which penetrated beyond one third of its thickness, simulating in vivo microtrauma. Rapid lateral spread of HSV1 to a mean of 13 keratinocytes wide occurred after 24 hours and free virus particles were observed between keratinocytes, consistent with an intercellular route of spread. Nectin-1 staining was markedly decreased in foci of infection in the epidermis and in the human keratinocyte HaCaT cell line. Nectin-1 was redistributed, at the protein level, in adjacent uninfected cells surrounding infection, inducible by CCL3, IL-8 (or CXCL8), and possibly CXCL10 and IL-6, thus facilitating spread. These findings provide the first insights into HSV1 entry and spread in human inner foreskin in situ.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Rana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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