IN-VIVO AND IN-VITRO EXPRESSION OF DEFECTIVE HEPATITIS-B VIRUS-PARTICLES GENERATED BY SPLICED HEPATITIS-B VIRUS-RNA

The mechanisms involved in hepatitis B virus (HBV) persistence are sti ll poorly understood. We have previously shown that the encapsidation of the singly spliced 2.2 kb-HBV RNA leads to the secretion of circula ting HBV defective particles in patients with chronic hepatitis, We ha ve now investigated the presence of the HBV defective particles in ser a from patients with acute and chronic hepatitis, using polymerase cha in reaction. These defective particles were detected in a larger amoun t in sera of patients with acute hepatitis that progressed to chronic hepatitis, or had already developed chronic hepatitis, as compared wit h those who recovered from acute hepatitis (the increase was estimated to be an average of 50-fold). In addition, we showed that the presenc e of these defective HBV particles is closely associated with the chro nic course of hepatitis B virus infection and with viral multiplicatio n. We also analyzed viral RNAs and proteins synthetized after in vitro transfection of Huh7 cell line with the corresponding defective hepat itis B virus DNA molecule. We showed that expression of the defective hepatitis B virus DNA alone leads to a marked intracellular accumulati on of the major core protein (HBcAg) and to an increased secretion of hepatitis B e antigen (HBeAg). These observations may be consistent wi th a role of these defective hepatitis B virus (HBV) particles in vira l persistence.