G. Natoli

The hepatitis B virus X protein transactivation of c-fos and c-myc proto-oncogenes is mediated by multiple transcription factors.

We have constructed two expression vectors in order to study the action of the HBV 17 Kd X protein on the c-fos and c-myc promoters. The results show that the promoters contain multiple elements that respond to X protein, suggesting involvement of multiple transcription factors. The exact mechanism of the interaction remains elusive, but our data allow speculation about the factors that may be influenced.

Detection of replicative intermediates of viral RNA in peripheral blood mononuclear cells from chronic hepatitis C virus carriers.

Clinical and experimental evidence suggests the possible existence of one or more extrahepatic sites of HCV infection. In order to demonstrate the in vivo infection of lymphoid cells by HCV, we applied a nested PCR to total cytoplasmic RNA extracted from fresh or cultured peripheral blood mononuclear cells (PBMCs) of HCV chronically infected patients, using primers derived from the highly conserved 5 untranslated region of the HCV genome. The presence of virions in PBMCs occurs frequently, if not always, and is often accompanied by active viral replication. Moreover, the appearance of replicative intermediates after stimulation of cellular growth with mitogens suggests that latent genomes could undergo replication upon cellular activation and/or proliferation.

Truncated pre-S/S proteins transactivate multiple target sequences

In order to investigate the transactivational function of HBV truncated preS/S proteins we have constructed two sets of plasmids and have tested their transactivational potential on the c-myc regulatory sequences and the TPA-responsive element. We found that preS/S proteins only become transactivationally active when truncated at the carboxy terminal end. Furthermore, using immunofluorescence microscopy we determined that the proteins are located exclusively in the cytoplasm, apparently ruling out DNA binding and activation of factors in the nucleus.