title: Herpesvirus chemokine-binding glycoprotein G (gG) efficiently inhibits neutrophil chemotaxis in vitro and in vivo.
abstract: Glycoprotein G (gG) of alphaherpesviruses has been described to function as a viral chemokine-binding protein (vCKBP). More recently, mutant viruses devoid of gG have been shown to result in increased virulence, but it remained unclear whether the potential of gG to serve as a vCKBP is responsible for this observation. In this study, we used equine herpesvirus type 1 (EHV-1) as a model to study the pathophysiological importance of vCKBP activity. First, in vitro chemotaxis assays studying migration of immune cells, an important function of chemokines, were established. In such assays, supernatants of EHV-1-infected cells significantly inhibited IL-8-induced chemotaxis of equine neutrophils. Identification of gG as the responsible vCKBP was achieved by repeating similar experiments with supernatants from cells infected with a gG-negative mutant, which were unable to alter IL-8-induced equine neutrophil migration. Furthermore, rEHV-1 gG was able to significantly reduce neutrophil migration, establishing gG as a bona fide vCKBP. Second, and importantly, in vivo analyses in a murine model of EHV-1 infection showed that neutrophil migration in the target organ lung was significantly reduced in the presence of gG. In summary, we demonstrate for the first time that EHV-1 gG not only binds to chemokines but is also capable of inhibiting their chemotactic function both in vitro and in vivo, thereby contributing to viral pathogenesis and virulence.
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Gerlinde R
authors.initials: GR
authors.lastname: Van de Walle
authors.forename: Maeva L
authors.initials: ML
authors.lastname: May
authors.forename: Woraporn
authors.initials: W
authors.lastname: Sukhumavasi
authors.forename: Jens
authors.initials: J
authors.lastname: von Einem
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Osterrieder
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D002464:Cell Migration Inhibition; D002474:Cell-Free System / Q000276:immunology; D018932:Chemokine CCL2 / Q000378:metabolism / Q000502:physiology; D018925:Chemokines / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004861:Herpesvirus 1, Equid / Q000276:immunology* / Q000472:pathogenicity; D006736:Horses; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D011024:Pneumonia, Viral / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000276:immunology; D011817:Rabbits; D014759:Viral Envelope Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014774:Virulence