Dr. Nikolaus Osterrieder
This proposal is a continuation and extension of our long-term efforts to determine the genomic regions and genes of Equine Herpesvirus Type 1 (EHV-1) that are involved in pathogenesis and determine tissue tropism in vivo . More specifically, our research has been focusing on the differences in membrane (glyco)protein and tegument protein genes between virulent and avirulent strains, because both groups of herpesvirus virus proteins that are constituents of the virus envelope (membrane (glyco)proteins) or the matrix (tegument proteins) have been shown to be crucially involved in cellular tropism and pathogenesis. In addition, we have been concentrating on how the knowledge of EHV-1 virulence factors can be exploited for the generation of efficacious and safe modified live vaccines. The presented proposal aims at two major goals. Firstly, studies are planned on continuing the analysis of the function of individual genes in different genetic virus backgrounds. Secondly, based on the notion that more recently the neuronal form of the disease with devastating sequelae has been observed, the immediate need has arisen to get a molecular handle on recent EHV-1 strains and isolates with putatively increased virulence and/or altered tropism. The severe neurological outbreaks that have occurred in the U.S. and the similar ones reported recently in the United Kingdom, Belgium and Germany have shown the need for extensive research into the pathobiology of EHV-1 infection. In addition, with the continuing threat of EHV-1 outbreaks despite regular vaccinations, the need for improved and novel vaccines that may be preferentially based on these novel EHV-1 isolates is even more pressing.