The AD38 cell line was created by stably transfecting HepG2 cells with a single copy of the cDNA of the pregenomic RNA (pgRNA) selleck kinase inhibitor of HBV under the control of the tetracycline-responsive cytomegalovirus promoter (18). In this system, pre-S and S mRNAs are expressed from two separate promoters on the viral genome, unlike pgRNA, and are not expected to be regulated by tetracycline. It is still possible that the increase in HBsAg in this model may have been secondary to direct activity of HIV on the tetracycline promoter. However, this is unlikely because a corresponding increase in HBV DNA via increased pgRNA transcription would be expected, and this was not evident. In addition, in other control experiments, VSV-NLNE had no effect on ��-galactosidase in AD43 cells, which is also under the control of the same tetracycline-responsive cytomegalovirus promoter (results not shown).

The mechanism(s) by which HIV infection may alter transcription or translation of the HBsAg is unknown. While it has been previously shown that the HBV X protein acts synergistically with the HIV Tat protein to induce HIV replication (15), the effect of this synergy on the HBV life cycle is unknown. It is possible that HIV directly influences transcription of the HBsAg mRNA, similar to the effect of the HBV X protein on HIV LTR transcription (25). Alternatively, there may be competition between HIV and HBV subviral particle secretion. HBV surface proteins and HIV gp160 envelope glycoprotein are membrane-associated proteins that are translated at the endoplasmic reticulum membrane.

There may be competition for host cellular machinery associated with secretion via multivesicular bodies such as ESCRT, Nedd4, Vps4B, or ALIX/AIP1, which are all thought to have a role in both HIV and HBV secretion (19, 23). This interaction may specifically affect HBV subviral particle secretion, which is thought to differ from virion secretion (19). Experiments to investigate this Batimastat interaction will form the basis of future studies. The absence of a direct effect on HBV replication in our studies was interesting, as HIV-HBV coinfection is associated with higher levels of HBV DNA in patients (11). This suggests that factors other than a direct HIV-HBV interaction are contributing to the increased HBV DNA levels in coinfected individuals. We demonstrated low-level HIV infection of HBV-expressing and nonexpressing hepatic cell lines. This was in contrast to previous studies where high levels of p24 were detected in culture supernatant following infection of hepatic cell lines with HIV (8). Cao and colleagues infected HepG2, Huh7, and Hep3B cells with CXCR4- and CCR5-using strains of HIV and demonstrated highly productive infection independent of CD4 (8).