Journal Article

Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

González-Motos, Víctor, Kropp, Kai A., Durán, Verónica, Sodeik, Beate, Lenac Rovis, Tihana, Verjans, Georges M. G. M., Viejo-Borbolla, Abel, Kalinke, Ulrich, Krey, Thomas, Jürgens, Carina, Ritter, Birgit, Proudfoot, Amanda E. I., Schulz, Thomas F., Binz, Anne, Bauerfeind, Rudolf, Rosenkilde, Mette M., Larsen, Olav, Ouwendijk, Werner J. D., Jonjic, Stipan, Kaufer, Benedikt B.

2017

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation / Adults / Animals / Anticoagulants / Artificial chromosomes / Biology / Biology and Life Sciences / Biotechnology / Cell Line / Cell lines / Cell migration / Cell Movement / Chemokine receptors / Chemokines / Chemokines - metabolism / Chicken pox / Chickenpox - immunology / Chickenpox - virology / Chronic infection / Chronic pain / Development and progression / Drosophila melanogaster / Embryology / Epithelial cells / Epithelial Cells - virology / Epithelium / Genes, Reporter / Genetic aspects / Glycoprotein C / Glycoproteins / Health aspects / Herpes zoster / Herpes Zoster - immunology / Herpes Zoster - virology / Herpesvirus 3, Human - genetics / Herpesvirus 3, Human - immunology / Herpesvirus 3, Human - physiology / Histology / Host-Pathogen Interactions / Humans / Immunology / Infections / Joint ventures / Latency / Leukocyte migration / Leukocytes / Leukocytes - physiology / Lymph nodes / Lymphatic system / Lymphocytes / Lymphocytes T / Medical schools / Medicine and Health Sciences / Monocytes / Mutation / Nervous system / Neutrophils / Pain / Palatine Tonsil - virology / Pathogenesis / Pathogens / Peripheral nervous system / Physiological aspects / Potentiation / Protein Domains / Proteins / Proteomics / Recruitment / Respiratory tract / Science / Signaling / T-Lymphocytes - virology / Tonsil / Varicella / Veterinary medicine / Viral Envelope Proteins - genetics / Viral Envelope Proteins - immunology / Viral Envelope Proteins - metabolism / Viral Proteins - genetics / Viral Proteins - metabolism / Virion / Virology / Viruses