The latency-associated transcript locus of herpes simplex virus 1 is a virulence determinant in human skin

Vanni, E. A.H. , Foley, J. W., Davison, A. J. , Sommer, M., Liu, D., Sung, P., Moffat, J., Zerboni, L. and Arvin, A. M. (2020) The latency-associated transcript locus of herpes simplex virus 1 is a virulence determinant in human skin. PLoS Pathogens, 16(12), e1009166. (doi: 10.1371/journal.ppat.1009166) (PMID:33370402) (PMCID:PMC7794027)

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Abstract

Herpes simplex virus 1 (HSV-1) infects skin and mucosal epithelial cells and then travels along axons to establish latency in the neurones of sensory ganglia. Although viral gene expression is restricted during latency, the latency-associated transcript (LAT) locus encodes many RNAs, including a 2 kb intron known as the hallmark of HSV-1 latency. Here, we studied HSV-1 infection and the role of the LAT locus in human skin xenografts in vivo and in cultured explants. We sequenced the genomes of our stock of HSV-1 strain 17syn+ and seven derived viruses and found nonsynonymous mutations in many viral proteins that had no impact on skin infection. In contrast, deletions in the LAT locus severely impaired HSV-1 replication and lesion formation in skin. However, skin replication was not affected by impaired intron splicing. Moreover, although the LAT locus has been implicated in regulating gene expression in neurones, we observed only small changes in transcript levels that were unrelated to the growth defect in skin, suggesting that its functions in skin may be different from those in neurones. Thus, although the LAT locus was previously thought to be dispensable for lytic infection, we show that it is a determinant of HSV-1 virulence during lytic infection of human skin.

Item Type:Articles
Additional Information:This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID; www.niaid.nih.gov/) (AI116857 granted to A.M.A.). The genome sequence analyses were supported by Medical Research Council (https://mrc.ukri.org/) grant MC_UU_12014/3 to A.J.D. J.M. is supported by an NIAID contract HHSN27220100030I. Stanford Cell Sciences Imaging Facility is supported, in part, by Award Number S10RR02557401 from the National Center for Research Resources (NCRR; https://orip.nih.gov/).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Vanni, Dr Emilia and Davison, Professor Andrew
Creator Roles:
Vanni, E.Conceptualization, Formal analysis, Methodology, Writing – original draft, Writing – review and editing
Davison, A. J.Formal analysis, Funding acquisition, Methodology, Writing – review and editing
Authors: Vanni, E. A.H., Foley, J. W., Davison, A. J., Sommer, M., Liu, D., Sung, P., Moffat, J., Zerboni, L., and Arvin, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in PLoS Pathogens 16(12):e1009166
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
Medical Research Council (MRC)MC_UU_12014/3