This contract combines a basic research emphasis and the molecular biology expertise of the group at the Division of Molecular Virology, Georgetown University, with the continuous programmatic monitoring and direction of DMID staff towards inclusion of state- of-the-art protocols from outside researchers which would otherwise not be achievable at a grant-funded level. The basic research focus continues to be the characterization of the Woodchuck Hepatitis Virus (WHV) infection as a model for human hepatitis B virus (HBV) infection and its long-term sequelae. New parameters of immunology, pathogenesis, and virology will be addressed during the contract period. Studies on the human hepatitis D virus (HDV) which coinfects WHV-infected woodchucks will be expanded to include potential vaccine studies as well as pathogenic analyses of different human HDV isolates. The differences between the Ground Squirrel Hepatitis Virus (GSHV) and WHV will be examined to identify genetic causes of variation in disease progression. The eventual goal from all these studies is to discern what determinants of viral infection lead to disease chronicity as opposed to disease recovery and where can interdiction take place to prevent the events leading to cirrhosis and hepatocellular carcinoma in hepatitis B patients.

Project Start
1993-10-16
Project End
1998-10-15
Budget Start
1997-09-29
Budget End
1998-08-27
Support Year
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Georgetown University
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Choo, Hyunah; Beadle, James R; Kern, Earl R et al. (2007) Antiviral activities of novel 5-phosphono-pent-2-en-1-yl nucleosides and their alkoxyalkyl phosphonoesters. Antimicrob Agents Chemother 51:611-5
Painter, George R; Almond, Merrick R; Trost, Lawrence C et al. (2007) Evaluation of hexadecyloxypropyl-9-R-[2-(Phosphonomethoxy)propyl]- adenine, CMX157, as a potential treatment for human immunodeficiency virus type 1 and hepatitis B virus infections. Antimicrob Agents Chemother 51:3505-9
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
Korba, Brent E; Cote, Paul J; Menne, Stephan et al. (2004) Clevudine therapy with vaccine inhibits progression of chronic hepatitis and delays onset of hepatocellular carcinoma in chronic woodchuck hepatitis virus infection. Antivir Ther 9:937-52
Wang, Y; Jacob, J R; Menne, S et al. (2004) Interferon-gamma-associated responses to woodchuck hepatitis virus infection in neonatal woodchucks and virus-infected hepatocytes. J Viral Hepat 11:404-17
Menne, Stephan; Cote, Paul J (2004) Measurement of cell-mediated immune response in woodchucks. Methods Mol Med 96:27-36
Wang, Yun; Menne, Stephan; Jacob, James R et al. (2003) Role of type 1 versus type 2 immune responses in liver during the onset of chronic woodchuck hepatitis virus infection. Hepatology 37:771-80
Menne, Stephan; Roneker, Carol A; Tennant, Bud C et al. (2002) Immunogenic effects of woodchuck hepatitis virus surface antigen vaccine in combination with antiviral therapy: breaking of humoral and cellular immune tolerance in chronic woodchuck hepatitis virus infection. Intervirology 45:237-50
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

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