Universität zu Köln

Rahn, Elena, Petermann, Philipp, Hsu, Mei-Ju, Rixon, Frazer J. and Knebel-Morsdorf, Dagmar (2011). Entry Pathways of Herpes Simplex Virus Type 1 into Human Keratinocytes Are Dynamin- and Cholesterol-Dependent. PLoS One, 6 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Herpes simplex virus type 1 (HSV-1) can enter cells via endocytic pathways or direct fusion at the plasma membrane depending on the cell line and receptor(s). Most studies into virus entry have used cultured fibroblasts but since keratinocytes represent the primary entry site for HSV-1 infection in its human host, we initiated studies to characterize the entry pathway of HSV-1 into human keratinocytes. Electron microscopy studies visualized free capsids in the cytoplasm and enveloped virus particles in vesicles suggesting viral uptake both by direct fusion at the plasma membrane and by endocytic vesicles. The ratio of the two entry modes differed in primary human keratinocytes and in the keratinocyte cell line HaCaT. Inhibitor studies further support a role for endocytosis during HSV-1 entry. Infection was inhibited by the cholesterol-sequestering drug methyl-beta-cyclodextrin, which demonstrates the requirement for host cholesterol during virus entry. Since the dynamin-specific inhibitor dynasore and overexpression of a dominant-negative dynamin mutant blocked infection, we conclude that the entry pathways into keratinocytes are dynamin-mediated. Electron microscopy studies confirmed that virus uptake is completely blocked when the GTPase activity of dynamin is inhibited. Ex vivo infection of murine epidermis that was treated with dynasore further supports the essential role of dynamin during entry into the epithelium. Thus, we conclude that HSV-1 can enter human keratinocytes by alternative entry pathways that require dynamin and host cholesterol.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rahn, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Petermann, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Hsu, Mei-Ju UNSPECIFIED UNSPECIFIED UNSPECIFIED Rixon, Frazer J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knebel-Morsdorf, Dagmar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-487358
DOI:	10.1371/journal.pone.0025464
Journal or Publication Title:	PLoS One
Volume:	6
Number:	10
Date:	2011
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POLARIZED EPITHELIAL-CELLS; COATED VESICLE FORMATION; LIPID RAFTS; MEDIATED ENDOCYTOSIS; LOW-PH; INHIBITION; ENDOSOMES; RECEPTOR; PROTEIN; ACTIN Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48735