Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway

Anthony V Nicola; Jean Hou; Eugene O Major; Stephen E Straus

doi:10.1128/JVI.79.12.7609-7616.2005

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Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway

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Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway

Anthony V Nicola, Jean Hou, Eugene O Major and Stephen E Straus

Journal of virology, Vol.79(12), pp.7609-7616

06/2005

DOI: https://doi.org/10.1128/JVI.79.12.7609-7616.2005

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https://hdl.handle.net/2376/110066

PMCID: PMC1143659

PMID: 15919913

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Abstract

Cell Line

Neurons - virology

Keratinocytes - virology

Protein-Tyrosine Kinases - metabolism

Humans

Epidermis - virology

Virion - metabolism

Endocytosis

Animals

Genistein - pharmacology

Herpesvirus 1, Human - pathogenicity

Epidermis - cytology

Hydrogen-Ion Concentration

Protein-Tyrosine Kinases - antagonists & inhibitors

Herpes simplex virus (HSV) enters some laboratory cell lines via a pH-dependent, endocytic mechanism. We investigated whether this entry pathway is used in human cell types relevant to pathogenesis. Three different classes of lysosomotropic agents, which raise endosomal pH, blocked HSV entry into primary and transformed human keratinocytes, but not into human neurons or neuroblastoma lines. In keratinocytes, incoming HSV particles colocalized with markers of endocytic uptake. Treatment with the isoflavone genistein, an inhibitor of protein tyrosine kinases, reduced the delivery of incoming viral particles to the nuclear periphery and virus-induced gene expression in keratinocytes but not neurons. Moreover, in keratinocyte monolayer islets, HSV infected both the inner and outer cells in a genistein-sensitive manner, suggesting viral endocytosis from both basolateral and apical plasma membrane surfaces. Together, the results indicate that HSV enters human epidermal keratinocytes, but not neurons, by a low-pH, endocytic pathway that is dependent on host tyrosine phosphorylation. Thus, HSV utilizes fundamentally different cellular entry pathways to infect important target cell populations.

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Title: Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway
Creators: Anthony V Nicola - Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1888, USA. anicola@niaid.nih.gov
Jean Hou
Eugene O Major
Stephen E Straus
Publication Details: Journal of virology, Vol.79(12), pp.7609-7616
Academic Unit: Veterinary Microbiology and Pathology, Department of
Publisher: United States
Identifiers: 99900547134101842
Language: English
Resource Type: Journal article