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Herpesvirus Chemokine-Binding Glycoprotein G (gG) Efficiently Inhibits Neutrophil Chemotaxis In Vitro and In Vivo¹

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Harry M. Zweig Memorial Fund for Equine Research at Cornell University.

² Address correspondence and reprint requests to Dr. Nikolaus Osterrieder, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. E-mail address: no34{at}cornell.edu

³ Abbreviations used in this paper: gG, glycoprotein G; MDV, Marek’s disease virus; vIL-8, viral IL-8; vCKBP, viral chemokine-binding protein; EHV, equine herpesvirus; p.i., postinfection; sgG, secreted gG; BAL, bronchioalveolar lavage; BAC, bacterial artificial chromosome.

This article has been cited by other articles:

				G. R. Van de Walle, K. W. Jarosinski, and N. Osterrieder Alphaherpesviruses and Chemokines: Pas de Deux Not Yet Brought to Perfection J. Virol., July 1, 2008; 82(13): 6090 - 6097. [Full Text] [PDF]

				G. R. Van de Walle, K. Sakamoto, and N. Osterrieder CCL3 and Viral Chemokine-Binding Protein gG Modulate Pulmonary Inflammation and Virus Replication during Equine Herpesvirus 1 Infection J. Virol., February 15, 2008; 82(4): 1714 - 1722. [Abstract] [Full Text] [PDF]