The contract at Cornell University has an excellent track record in the breeding and housing of the woodchuck animal model with great lengths taken to study all aspects of this model's infection by the woodchuck hepatitis virus (WHV). This woodchuck/WHV model closely parallels the disease progression produced in humans by the hepatitis B virus (HBV). Predictable numbers of infected pups are produced yearly for experiments such as: (1) the testing of natural and synthetic antivirals and immunomodulators against WHV in infected animals, (2) the study of the coinfection/superinfection of human hepatitis delta virus (HDV) and WHV for the development of HDV vaccines and antivirals, (3) the comparison of disease progression between WHV and the related ground squirrel hepatitis virus (GSHV) in the woodchuck -- the latter producing more cirrhosis and a slower progression to hepatocellular carcinoma, (4) the study of immunologic mechanisms triggered during the acute and chronic stages of the disease and detection of possible pathways to target for prevention of chronicity, and (5) the transfection of woodchuck livers by recombinant WHV DNA to pinpoint biologically important sequences. This contract's goals are to assist with the overall efforts of the Hepatitis Program in the prevention of Types B and D viral hepatitis. Even though safe and effective vaccines are presently available for HBV, there are still over a million chronic carriers of hepatitis B in the U.S. alone. Specifically there is the potential for the eradication of long term complications such as chronic hepatitis B and D liver disease and primary hepatocellular carcinoma by immunization, immunologic methods, or therapeutic treatments.

Project Start
1993-05-16
Project End
1999-07-02
Budget Start
1999-07-02
Budget End
1999-09-29
Support Year
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Casey, John L; Tennant, Bud C; Gerin, John L (2006) Genetic changes in hepatitis delta virus from acutely and chronically infected woodchucks. J Virol 80:6469-77
Casey, John; Cote, Paul J; Toshkov, Illia A et al. (2005) Clevudine inhibits hepatitis delta virus viremia: a pilot study of chronically infected woodchucks. Antimicrob Agents Chemother 49:4396-9
Jacob, James R; Sterczer, Agnes; Toshkov, Ilia A et al. (2004) Integration of woodchuck hepatitis and N-myc rearrangement determine size and histologic grade of hepatic tumors. Hepatology 39:1008-16
Tatti, Kathleen M; Korba, Brent E; Stang, Heather L et al. (2002) Mutations in the conserved woodchuck hepatitis virus polymerase FLLA and YMDD regions conferring resistance to lamivudine. Antiviral Res 55:141-50
Menne, Stephan; Roneker, Carol A; Roggendorf, Michael et al. (2002) Deficiencies in the acute-phase cell-mediated immune response to viral antigens are associated with development of chronic woodchuck hepatitis virus infection following neonatal inoculation. J Virol 76:1769-80
Nagy, Tamas; McDonough, Sean P; Erb, Hollis N et al. (2002) Lymphosarcoma in the laboratory woodchuck (Marmota monax). Comp Med 52:152-9
Menne, Stephan; Roneker, Carol A; Korba, Brent E et al. (2002) Immunization with surface antigen vaccine alone and after treatment with 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)-uracil (L-FMAU) breaks humoral and cell-mediated immune tolerance in chronic woodchuck hepatitis virus infection. J Virol 76:5305-14
Hurwitz, Selwyn J; Tennant, Bud C; Korba, Brent E et al. (2002) Viral pharmacodynamic model for (-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine (emtricitabine) in chronically infected woodchucks. Antivir Chem Chemother 13:165-76
Sahu, Gautam Kumar; Tai, Pei-Ching; Chatterjee, Soma Banerjee et al. (2002) Out-of-frame versus in-frame core internal deletion variants of human and woodchuck hepatitis B viruses. Virology 292:35-43
Concannon, P; Levac, K; Rawson, R et al. (2001) Seasonal changes in serum leptin, food intake, and body weight in photoentrained woodchucks. Am J Physiol Regul Integr Comp Physiol 281:R951-9

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