Precore-mediated inhibition of hepatitis B virus progeny DNA synthesis.

摘要: The capacities to induce the synthesis of hepatitis B virus (HBV) unit-length DNA were compared for two HBV DNAs with an overall sequence diversity about 10%. They had been cloned from serum (DNA2) and a hepatocellular carcinoma (DNA4), respectively. As major difference, DNA4 carries translational stop signal preventing precore protein. Progeny yields obtained after transfection respective pregenome transcription units allocated DNA2 low-replicator high-replicator phenotype. Cotransfection interfered progeny induced by DNA4. By mutual exchange restriction fragments, region on viral genome responsible differing replicator phenotypes was confined comprising 3'-terminal part X gene, core promoter, encapsidation epsilon, precore/core 5'-terminal pol gene. Point mutations in abolishing proper expression gene strongly enhanced yield DNA, whereas cotransfection plasmid or mutated substantially lowered amount DNA. Hence, acts as inhibitory principle replication. same mutation has found arise frequently carriers. Loss concomitant conversion more severe hepatitis, observed course chronic infection, thus can be explained relaxation replication-level control.