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Klaus Osterrieder
Dr. Osterrieder assumed his position as Associate Professor of Virology within the Department of Microbiology and Immunology in August 2002. His previous experience was as a group leader at the Institute of Molecular Biology, Federal Research Center for Virus Diseases of Animals in Insel Riems, Germany, where he had worked since 1997. He received a DVM degree from Ludwig-Maximilians-University in Munich, Germany, in 1990 and finished his dissertation in 1992 at the same university. He held a position at the Institute for Medical Microbiology at the Veterinary Faculty of the Ludwig-Maximilians-University, where he was awarded the 'Habilitation' in 1997, prior to moving to Insel Riems. His research program is currently supported by the NIH for work on varicella zoster virus (VZV), the USDA for his program on Marek's disease virus (MDV), and by the Morris Animal Foundation and the Harry M. Zweig Memorial Fund for work on equine herpesvirus type 1 (EHV-1). Research Interests / Lab Members / Related Links / Selected References Generally spoken, the research interests of my laboratory focus on the interaction between the human herpesvirus varicella zoster virus (VZV) as well as the animal herpesviruses equine herpesvirus type 1 (EHV-1) and Marek's disease virus (MDV) and the host cell or organism, respectively. VZV causes chicken pox in infants and shingles in adults. EHV-1 causes respiratory disease, neurological signs and abortions in horses, while MDV is a tumorigenic virus causing a deadly T cell lymphoproliferative disease in the domestic chicken. More specifically, we try to unravel the function of proteins of distinct subviral components in the life cycle of herpesviruses. These important pathogens consist of a nucleocapsid that contains the double-stranded linear DNA genome, a matrix (the so-called tegument) consisting of numerous proteins, and an envelope derived from cellular membranes, in which viral (glyco)proteins are incorporated. We study the role of viral envelope (glyco)proteins as well as the tegument proteins in the early entry steps of virus infection and in the egress of newly synthesized virions from infected cells. The role of individual open reading frames in the viruses' life cycles is assessed primarily by constructing and analyzing virus mutants. Our laboratory generates EHV-1 and MDV mutants by homologous recombination in cultured eukaryotic cells or - more recently - by mutagenesis of EHV-1 and MDV genomes cloned as so-called bacterial artificial chromosomes in Escherichia coli. We have cloned several EHV-1 and MDV strains as infectious genomes using this technique and apply RecA- and RecE/T-based mutagenesis in E. coli to manipulate the viral genomes. Analysis of numerous EHV-1 and MDV mutants revealed that the two closely related viruses express similar sets of envelope and tegument (glyco)proteins. Recently, we have initiated a program targeted towards the establishment of infectious BAC clones for virulent and avirulent VZV strains in order to perform studies similar to those done for EHV-1 and MDV. The aim for the VZV program will both extend and supplement studies in the EHV-1 and MDV system, and virus mutants are analyzed in greater detail for their behavior in cultured cells and concerning the interaction of viral proteins with proteins of various subcellular compartments. Our interests also extend to identifying genomic regions of VZV, EHV-1 and MDV, which are responsible for virulence. In addition, we seek to develop and improve vaccines and vaccine regimens against infections with these important human and animal pathogens. The vaccines are based on generation of modified live vaccines and on DNA vaccinations using the developed VZV, EHV-1 and MDV BACs. Another focus of the laboratory is to develop EHV-1 into a universal vector for immunization and gene therapy, because we have recently discovered that EHV-1 can efficiently enter primary cells of bovine, porcine and -most importantly - human origin. In addition, EHV-1 does not induce long-lasting immunity, and pre-exisiting antibodies in the human population have not been detected. In a first step, we will express immunogenic proteins of model human and animal virus pathogens (HIV, hepatitis C virus, West Nile virus, Venezuelan equine encephalitis virus, bovine viral diarrhea virus), and determine the expression levels, vector stability and the induction of an immune response in animal models.
Dr. Osterrieder is a member of the following Graduate Fields:
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Selected References (for a complete list, click here) Osterrieder, N., Neubauer, A., Brandmüller, C., Kaaden, O.-R. and O'Callaghan, D.J. (1996). The equine herpesvirus 1 (EHV-1) IR6 protein influcences virus growth at elevated temperatures and is a major determinant of virulence. Virology 226, 243-251. Schumacher, D., Tischer, B.K., Fuchs, W. and Osterrieder, N. (2000). Reconstitution of Marek's Disease Virus serotype 1 (MDV-1) from DNA cloned as a bacterial artificial chromosome (BAC) and characterization of a glycoprotein B-negative MDV-1 mutant. Journal of Virology 74:11088-11098. Tischer, B.K., von Einem, J., Kaufer, B., and Osterrieder N. (2006). Two-step Red-mediated recombination for versatile, high-efficiency markerless DNA manipulation in Escherichia coli. BioTechniques 40: 191-196. Osterrieder, N., Kamil, J.P., Schumacher, D., Tischer, B.K., and Trapp, S. (2006). Marek’s disease – From Miasma to Model. Nature Reviews Microbiology 4: 283-294. Goodman, L.B. Wagner, B., Flaminio, M.F., Sussman, K.H., Metzger, S.M., Holland, R., and Osterrieder, N. (2006). Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type 1 (EHV-1). Vaccine 24, 3636-3645. Trapp, S., Kamil, J.P., Schumacher, D., Nair, V.K., Parcells, M.S., and Osterrieder, N. (2006). A Virus-Encoded Telomerase RNA Promotes Malignant T-Cell Transformation. The Journal of Experimental Medicine 203, 1307-1317.
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