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HSV1 Enters Human Keratinocytes by a Nectin-1-Dependent, Rapid Plasma Membrane Fusion Pathway that Functions at Low Temperature

Sayers, CL and Elliott, GD (2016) HSV1 Enters Human Keratinocytes by a Nectin-1-Dependent, Rapid Plasma Membrane Fusion Pathway that Functions at Low Temperature Journal of Virology.

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Abstract

Herpes simplex virus 1 (HSV1) infects humans through stratified epithelia that are composed primarily of keratinocytes. The route of HSV1 entry into keratinocytes has been the subject of limited investigation, but is proposed to involve pH-dependent endocytosis, requiring the gD-binding receptor, nectin-1. Here, we have utilized the nTERT human keratinocyte cell line as a new model for dissecting the mechanism of HSV1 entry in to the host. Although immortalised, these cells nonetheless retain normal growth and differentiation properties of primary cells. Using siRNA depletion studies, we confirm that, despite nTERT cells expressing high levels of the alternative gD receptor HVEM, HSV1 requires nectin-1, not HVEM, to enter these cells. Strikingly, virus entry into nTERT cells occured with unusual rapidity, such that maximum penetration was achieved within 5 minutes. Moreover, HSV1 was able to enter keratinocytes but not other cell types at temperatures as low as 7°C, conditions where endocytosis was shown to be completely inhibited. Transmission electron microscopy of early entry events at both 37°C and 7°C identified numerous examples of naked virus capsids located immediately beneath the plasma membrane, with no evidence of virions in cytoplasmic vesicles. Taken together, these results imply that HSV1 uses the nectin-1 receptor to enter human keratinocyte cells via a previously uncharacterised rapid plasma membrane fusion pathway that functions at low temperature. These studies have important implications for current understanding of the relationship between HSV1 and its relevant in vivo target cell.

Item Type: Article
Subjects : Medical Science
Authors :
AuthorsEmailORCID
Sayers, CLUNSPECIFIEDUNSPECIFIED
Elliott, GDUNSPECIFIEDUNSPECIFIED
Date : 2016
Copyright Disclaimer : Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Depositing User : Symplectic Elements
Date Deposited : 07 Sep 2016 12:10
Last Modified : 07 Sep 2016 12:10
URI: http://epubs.surrey.ac.uk/id/eprint/812013

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