2017

Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

González-Motos V, Jürgens C, Ritter B, Kropp K, Durán V, Larsen O, Binz A, Ouwendijk W, Lenac Rovis T, Jonjic S, Verjans G, Sodeik B, Krey T, Bauerfeind R, Schulz T, Kaufer B, Kalinke U, Proudfoot A, Rosenkilde M, Viejo-Borbolla A

Published in

PLoS pathogens: Volume 13, Issue 5, Page e1006346

Abstract

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.

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Cite this publication

DOI: 10.1371/journal.ppat.1006346

Authors

Ulrich Kalinke

Prof. Dr. Ulrich Kalinke

Executive Director