TY - JOUR
T1 - Interrupted replication of hepatitis B virus in liver tissue of HBsAg carriers with hepatocellular carcinoma
AU - Raimondo, Giovanni
AU - Burk, Robert D.
AU - Lieberman, Harvey M.
AU - Muschel, Joseph
AU - Hadziyannis, Stephanos J.
AU - Will, Hans
AU - Kew, Michael C.
AU - Dusheiko, Geoffrey M.
AU - Shafritz, David A.
N1 - Funding Information:
Research supported in part by NIH Grants CA 32605 (DAS), CA 45476 (RDB), and P-50 DK 17702, the Gail I. Zuckerman Foundation, and the Marion Bessin Liver Center Fund. Dr. G. Raimondo was supported in part by the University of Messina, Messina, Italy, and by a grant from the Associazione ltaliana per la Ricerca sul Cancro. Dr. H. Will was supported in part by a grant (Wi 66412-l) from the Deutsche Forschungsgemeinschaft. Drs. H. Lieberman and R. D. Burk were recipients of N.I.H. Clinical Investigator Awards K08-DK 01390 and KO&CA 00983, respectively. The authors also thank Mr. Roy Forbes and Ms. Anna Caponigro for preparation of the manuscript.
PY - 1988/9
Y1 - 1988/9
N2 - To search for events underlying reduction of peripheral viremia and integration of hepatitis B virus (HBV) DNA into the liver cell genome in long-term virus carriers with hepatocellular carcinoma, paired samples of liver and tumor tissue were analyzed by molecular hybridization and immunological methods. Most tumor tissues contained integrated viral DNA; in none was extrachromosomal HBV DNA detected. Integrated HBV DNA was also found in peritumor liver tissue in the majority of patients. However, liver of patients either with or without peripheral viremia also contained free HBV DNA and replicative intermediates. In three nonviremic patients with replicative HBV DNA in liver, viral core antigen expression was markedly reduced or absent, whereas viral envelope protein (surface antigen) expression was normal. In one case, replicative intermediates in liver were sensitive to DNase I digestion, indicating that viral DNA was not encapsidated in normal viral core particles. These results suggest that decreased or defective core antigen production can lead to reduced viremia associated with blocked virus assembly/secretion and accumulation of unencapsidated HBV DNA replicative intermediates in the liver cell. Accumulation of such HBV DNA molecular forms in the liver may lead to an increased propensity for HBV DNA to integrate into the host genome, which has been found with high frequency in hepatic neoplasms from patients infected with hepatitis B virus.
AB - To search for events underlying reduction of peripheral viremia and integration of hepatitis B virus (HBV) DNA into the liver cell genome in long-term virus carriers with hepatocellular carcinoma, paired samples of liver and tumor tissue were analyzed by molecular hybridization and immunological methods. Most tumor tissues contained integrated viral DNA; in none was extrachromosomal HBV DNA detected. Integrated HBV DNA was also found in peritumor liver tissue in the majority of patients. However, liver of patients either with or without peripheral viremia also contained free HBV DNA and replicative intermediates. In three nonviremic patients with replicative HBV DNA in liver, viral core antigen expression was markedly reduced or absent, whereas viral envelope protein (surface antigen) expression was normal. In one case, replicative intermediates in liver were sensitive to DNase I digestion, indicating that viral DNA was not encapsidated in normal viral core particles. These results suggest that decreased or defective core antigen production can lead to reduced viremia associated with blocked virus assembly/secretion and accumulation of unencapsidated HBV DNA replicative intermediates in the liver cell. Accumulation of such HBV DNA molecular forms in the liver may lead to an increased propensity for HBV DNA to integrate into the host genome, which has been found with high frequency in hepatic neoplasms from patients infected with hepatitis B virus.
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U2 - 10.1016/0042-6822(88)90151-1
DO - 10.1016/0042-6822(88)90151-1
M3 - Article
C2 - 2842938
AN - SCOPUS:0023789344
SN - 0042-6822
VL - 166
SP - 103
EP - 112
JO - Virology
JF - Virology
IS - 1
ER -