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    Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration (2017)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    González-Motos, Víctor
    Jürgens, Carina
    Ritter, Birgit
    Kropp, Kai A
    Durán, Verónica
    Larsen, Olav
    Binz, Anne
    Ouwendijk, Werner J D
    Lenac Rovis, Tihana
    Jonjic, Stipan
    Verjans, Georges M G M
    Sodeik, Beate
    Krey, Thomas
    Bauerfeind, Rudolf
    Schulz, Thomas F
    Kaufer, Benedikt B (WE 5)
    Kalinke, Ulrich
    Proudfoot, Amanda E I
    Rosenkilde, Mette M
    Viejo-Borbolla, Abel
    Quelle
    PLoS Pathogens; 13(5) — S. e1006346
    ISSN: 1553-7366
    Sprache
    Englisch
    Verweise
    DOI: 10.1371/journal.ppat.1006346
    Pubmed: 28542541
    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

    Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZV systemic dissemination in humans.