The cytoplasmic HBVDNA implication: HBV replication or non-replicative status

Abstract

Intrahepatocellular HBVDNA was investigated in patients with chronic hepatitis B by in situ hybridization assay, employing biotin-labelled HBVDNA as the specific probe. It was found that HBVDNA was predominantly present in the cytoplasm of hepatocytes. In general the cases with cytoplasmic HBVDNA could be grouped as follows: 1) cytoplasmic HBVDNA coinciding with intrahepatic envelope protein and nucleocapsid component expression, this pattern of the cytoplasmic HBVDNA would be replicative; 2) cytoplasmic HBVDNA accompanied by intrahepatic single HBsAg expression, common to HBVDNA integrated into host genome with only HBsAg being found frequently in liver; 3) with only cytoplasmic HBVDNA, with neither HBsAg nor HBcAg expression, representative for non-replicative status. It is speculated that the reason for the occurrence of the cytoplasmic hybridization signal in cases with non-replicative HBVDNA may be due to DNA-RNA transcript hybrid. The prudent way to evaluate the implication of the cytoplasmic HBVDNA is to consider the combination of HBVDNA location, intrahepatic gene product expression, and HBV markers in the serum.

Keywords

HBVDNA / viral replication / DNA transcript / in situ hybridization / DNA-RNA hybrid

References

[1] NegroF, et al.. Detection of HBVDNA by in situ hybridization using a biotinlabelled probe. J Med Virol, 1985, 15: 373-82

[2] RijntjesPJM, et al.. Hepatitis B virus DNA detected in formalin-fixed liver specimens and its relation to serological markers and histopathological features in chronic liver disease. AJP, 1985, 120: 411-8

[3] International Group. Acute and chronic hepatitis revised. Lancet, 1977, I: 914-7

[4] ZhangYY, et al.. Morphology, distribution and its significance of intrahepatic HBVDNA in liver disease: a study by in situ hybridization. J Tongji Med Univ, 1989, 9: 204-9

[5] BoninoF. The importance of hepatitis B viral DNA in serum and liver. J Hepatol, 1986, 3: 136-41

[6] BrechotC, et al.. Hepatitis B viral sequences in the infected tissues. Progr Clin Biol Res, 1983, 5: 431-4

[7] TanakaY, et al.. Frequent integration of hepatitis B virus DNA in noncancerous liver tissues from hepatocellular carcinoma patients. J Med Vicol, 1988, 26: 7-14

[8] Bonino F, et al. Serological markers of HBV infectivity. Ann 1st Super Sanita 1988; 217–24.

[9] MichelML, TiollasP. Structure and expression of the hepatitis B virus genome. Hepatology, 1987, 7: 61s-3s

[10] MillerRH, et al.. Compact organization of the hepatitis B virus genome. Hepatology, 1989, 9: 322-7

[11] SuTS, et al.. Analysis of hepatitis B virus transcripts in infected human liver. Hepatology, 1989, 9: 180-5

[12] ChenJY, et al.. Detection of hepatitis B virus DNA in hepatocellular carcinoma: methylation of integrated viral DNA. J Virol Methods, 1988, 19: 257-63

[13] RamalhoF, et al.. Serum markers of hepatitis B virus replication, liver histology and intrahepatic expression of hepatitis B core antigen. J Hepatol, 1988, 7: 1-7