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    Glycoprotein H and α4β1 integrins determine the entry pathway of alphaherpesviruses (2013)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Azab, Walid (WE 5)
    Lehmann, Maik J
    Osterrieder, Nikolaus (WE 5)
    Quelle
    Journal of virology; 87(10) — S. 5937–5948
    ISSN: 0022-538x
    Sprache
    Englisch
    Verweise
    DOI: 10.1128/JVI.03522-12
    Pubmed: 23514881
    Kontakt
    Institut für Virologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
    Tel. +49 30 838 51833 Fax. +49 30 838 451847
    email:viro@zedat.fu-berlin.de

    Abstract / Zusammenfassung

    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 α4β1 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 α4β1 integrins are important determinants in the choice of alphaherpesvirus cellular entry pathways.