Immunmodulation und Beeinflussung der Virulenz durch das vom Equinen Herpesvirus vo, Typ 1 (EHV-1) kodierte Glykoprotein G (gG)

• Antragsteller: Professor Dr. Nikolaus Osterrieder
• Fachliche Zuordnung: Tiermedizin
• Förderung: Förderung von 2007 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 63321424

This proposal is part of our long-term efforts to analyze the contributions of individualgene products of equine herpesvirus type 1 (EHV-1), which are involved in virulence andpathogenesis and/or are important for immune protection. Recently, our research hasfocused on secreted EHV-1 gene products, among them glycoprotein G (gG). This viralglycoprotein is found both in cellular and viral membranes and is secreted from infectedcells. EHV-1 gG has been shown to function as a viral chemokine binding protein (vCKBP)and studies in mice, using an EHV-1 virus devoid of gG, have demonstrated a significanteffect on migration of immune cells within the target organ, the lung. The results indicate animportant role of gG in pathogenesis. In this context it is important to note that gG of theclosely related but less pathogenic EHV-4 does not display vCKBP activity, although bothmolecules share 68% sequence identity. We will test the hypothesis that a variableregion in the extracellular domain of gG is responsible for chemokine binding andimportant for EHV-1 virulence. The hypothesis is tested by two specific aims that will 1)generate chimeric molecules between EHV-1 and EHV-4 gG to identify the vCKBP domainand 2) generate recombinant viruses harboring various forms of EHV-1 gG, which will betested in a murine model of EHV-1 infection and, ultimately, in horses. Knowledge withrespect to putative EHV-1 virulence factors is indispensable for the rational design andgeneration of efficacious and safe modified live vaccines against one of the economicallymost important and devastating viral diseases of the horse.

• DFG-Verfahren: Sachbeihilfen