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Principal Investigator: Dr. Jeremy Kamil
Mentor: Dr. Klaus Osterrieder
Contact Information: E-mail: jpk3@cornell.edu - Phone: 3-4067
Sponsor: USDA - NRI Competitive Grant - Postdoctoral Fellowship
Grant Number: 2004-35204-14653
Title: Role of a Viral Lipase Homolog in Marek's Disease Pathogenesis
Annual Direct Cost: $52,823
Project Period: 9/1/04 - 8/31/06
Marek's disease virus (MDV) is a herpesvirus pathogen of chickens which causes a devastating T-cell lymphoma associated disease. The MDV genome encodes a protein, vLIP, which bears significant homology to pancreatic lipases and is the first example of a herpesvirus lipase homolog. Homologues of vLIP are also present in several avian adenoviruses. This study will evaluate whether vLIP is a determinant of MDV pathogenesis and whether vLIP covalently bonds fatty acids.
We will assess the role of vLIP, a viral lipase homolog, in the pathogenesis of Marek's disease. Marek's disease virus (MDV) causes an aggressive T-cell lymphoma associated disease in infected chickens. We hypothesize that vLIP mutant viruses may show a reduced incidence of Marek's disease in vivo. Our first objective is to test this hypothesis directly by comparing pathogenesis of vLIP mutant viruses against wild type viruses in experimentally infected chickens. We also wish to directly assess the biochemical functions of vLIP in viral replication. While we have already established in preliminary experiments that vLIP is not likely to serve as a conventional lipase enzyme, we hypothesize that vLIP instead fosters covalent bonds to fatty acids via its serine nucleophile. In our second objective, we will perform in vitro studies on recombinant vLIP protein to assess whether covalently bound fatty acids can be detected at the serine nucleophile position. As vLIP homologues are well conserved throughout the Marek's disease-like genus of herpesviruses, and are also encoded by several avian adenoviruses, we hope that these studies will lead to a better understanding of the function of this group of pancreatic lipase homologues in avian DNA viruses. We also hope that the elucidation of the role of vLIP in MDV pathogenesis may also inform future efforts at vaccine construction.
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