Detection of Hepatitis B Virus-specific DNA in the Genomes of Human Hepatocellular Carcinoma and Liver Cirrhosis Tissues

Abstract

SUMMARYHepatitis B virus-related DNA was detected in the chromosomal DNA of three out of seven hepatocellular carcinomas and two out of five cirrhosis samples examined, by means of the blot-hybridization technique, described by Southern (1975). The integration patterns were not identical but some similarities raise the question of whether there are some preferred sites of viral integration.

Residual integrated viral DNA after hepadnavirus clearance by nucleoside analog therapy

“…It has been proposed that the removal of cccDNA occurs by hepatocyte turnover, and that dilution of cccDNA copy numbers in dividing hepatocytes results in eventual segregation of uninfected progeny cells (12). Alternatively, uninfected hepatocytes may arise by differentiation of uninfected progenitors (13) or be generated through a slow loss of cccDNA from infected hepatocytes (14,15).During hepadnavirus infection, a small fraction of hepatocytes undergo recombination with viral DNA molecules in the nucleus and acquire an integrated viral DNA that may be stably retained in that hepatocyte lineage (16)(17)(18)(19)(20). The common precursor to integrated viral DNA is a full-length linear double-stranded DNA, with a left end just upstream of the viral core gene, that is formed as a by-product of viral genome synthesis (21,22).…”

The hepatitis B virus X protein up-regulates tumor necrosis factor α gene expression in hepatocytes

“…1 In this context, it has been shown that most HBV-related hepatocellular carcinomas contained integrated viral DNA. 2 Four genes are encoded by the viral genome: S/preS, C/preC, P, and X. 3 The X gene encodes a 17-kd protein, termed HBx, that has been shown to function as a transcriptional trans-activator of a variety of viral and cellular promoter/enhancer elements.…”

Evidence for Non-chromosomal Hepatitis B Virus Surface (HBsAg)- and Core Antigen (HBcAg)-specific DNA Sequences in a Hepatoma Cell Line

“…Thus, HBV-specific DNA is present not only in nuclei of the cells (Marion et aL, 1980;Chakraborty et al, 1980;Brechot et al, 1980;Edman et aL, 1980;Koshy et al, 1981) but also in a non-chromosomal form. Since chromosomal DNA of these cells contains integrated virus genes not only for HBsAg (which is synthesized in the cells) but very probably the complete virus genome (Marion et al, 1980), one could envisage the presence of additional HBV sequences also in the beta particle DNA.…”

“…Particulate material from the latter was further concentrated by pelleting through a 10% sucrose cushion and is subsequently referred to as beta particles. The beta particles as well as fractions containing nuclei or mitochondria were submitted to a gentle DNA extraction procedure (Koshy et al, 1981). Two recombinant plasmids (Burrell et al, 1979), pHBV 20 [with a 650 base pair (bp) insert specific for HBsAg] and pHBV 8.2.51 (with a 550 bp insert specific for HBcAg), have been kindly provided by Dr K. Murray, Heidelberg, F.R.G.…”

“…DNA is present in PLC/PRF/5 cells appears to contradict results published by others, but in fact does not. The material we used in the study consisted of concentrated particles from the post-mitochondrial supernatant of the cells, while others either used one of the bands from total cellular DNA formed in CsC1 gradients (Marion et aI., 1980) or purified nuclei (Chakraborty et al, 1980;Koshy et al, 1981) or total cellular DNA (Brechot et al, 1980;Edman et al, 1980). Therefore, the results cannot be compared.…”