Publikationsdatenbank

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
+49 30 838 51833
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.