Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

PLoS Pathogens

Georges M. G. M. Verjans¹  Stipan Jonjic¹  Anne Binz²  Tihana Lenac Rovis³  Beate Sodeik³  Ulrich Kalinke⁴  Thomas F. Schulz⁴  Abel Viejo-Borbolla⁴  Olav Larsen⁵  Birgit Ritter⁶  Víctor González-Motos⁶  Benedikt B. Kaufer⁶  Mette M. Rosenkilde⁶  Verónica Durán⁶  Rudolf Bauerfeind⁶  Kai A. Kropp⁶  Werner J. D. Ouwendijk⁶  Thomas Krey⁷  Amanda E. I. Proudfoot⁸  Carina Jürgens⁹ 

[1] Center for Proteomics and Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia;Department of Biomedical Sciences, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark;Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands;German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany;Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany;Institute of Virology, Hannover Medical School, Hannover, Germany;Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany;Research Core Unit for Laser Microscopy, Hannover Medical School, Hannover, Germany;University of Veterinary Medicine Hannover, Foundation, Hannover, Germany

关键词: Chemokines;    White blood cells;    Recombinant proteins;    Chemotaxis;    Heparin;    Cell migration;    T cells;    Insects;   

DOI  :  10.1371/journal.ppat.1006346

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY