The Molecular Basis of Viral Replication and Pathogenesis 
ilar in vitro reconstruction reactions are being 
attempted for the reverse transcription reaction 
itself. This enormously complex reaction gener- 
ates the duplex DNA genome from its RNA pre- 
cursor. By fully characterizing the molecules that 
catalyze the reaction and the intermediates 
through which it proceeds, we hope to identify 
novel targets for drugs that would be useful in 
interrupting virus growth. 
The development of liver cancer during persis- 
tent infection is another major focus of interest. 
For this we study two relatives of HBV: the wood- 
chuck hepatitis virus (WHV), which is potently 
oncogenic in its normal host, and the ground 
squirrel hepatitis virus (GSHV), a less-efficient 
carcinogenic stimulus in woodchucks. Our stud- 
ies thus far suggest fundamental differences in 
the oncogenic pathways employed by these 
closely related viruses. WHV-induced tumors fre- 
quently (30-45 percent) contain integrated 
WHV genomes adjacent to the N-myc oncogene, 
whose expression is thereby activated. Such in- 
sertional activation is not apparent in GSHV- 
induced hepatomas. We are currently looking for 
other genes that are regularly disrupted by WHV 
integration, with the view that such loci may de- 
fine other proteins centrally involved in the con- 
trol of normal hepatocyte growth. 
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