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Glycoprotein H and alpha 4 beta 1 Integrins Determine the Entry Pathway of Alphaherpesviruses
Faculty
Veterinary Medicine
Year:
2013
Type of Publication:
Article
Pages:
5937-5948
Authors:
Azab, Walid, Lehmann, Maik J, Osterrieder, Nikolaus
DOI:
10.1128/JVI.03522-12
Journal:
JOURNAL OF VIROLOGY AMER SOC MICROBIOLOGY
Volume:
87
Research Area:
Virology
ISSN
ISI:000318155000053
Keywords :
Glycoprotein , , alpha , beta , Integrins Determine , Entry
Abstract:
Herpesviruses enter cells either by direct fusion at the plasma membrane or from within endosomes, depending on the cell type and receptor(s). We investigated two closely related herpesviruses of horses, equine herpesvirus type 1 (EHV-1) and EHV-4, for which the cellular and viral determinants routing virus entry are unknown. We show that EHV-1 enters equine epithelial cells via direct fusion at the plasma membrane, while EHV-4 does so via an endocytic pathway, which is dependent on dynamin II, cholesterol, caveolin 1, and tyrosine kinase activity. Exchange of glycoprotein H (gH) between EHV-1 and EHV-4 resulted in rerouting of EHV-1 to the endocytic pathway, as did blocking of alpha 4 beta 1 integrins on the cell surface. Furthermore, a point mutation in the SDI integrin-binding motif of EHV-1 gH also directed EHV-1 to the endocytic pathway. Cumulatively, we show that viral gH and cellular alpha 4 beta 1 integrins are important determinants in the choice of alpha-herpesvirus cellular entry pathways.
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