The hepatitis B virus X protein induces HIV-1 replication and transcription in synergy with T-cell activation signals - Functional roles of NF-kappa B/NF-AT and SP1-binding sites in the HIV-1 long terminal repeat promoter

Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus type-1 (HIV-1) is relatively common. However, the impact of this co-infecti on on the clinical outcome of HIV infection has not been elucidated. We her ein demonstrate that the HBV X protein (HBx) superinduces ongoing HIV-1 rep lication and HIV-1 long terminal repeat (LTR) transcription by synergizing with Tat protein and with T-cell activation signals. Although HBx cooperate d with mitogenic stimuli in the induction of reporter plasmids harboring th e HIV-1 kappaB enhancer, in both a NF-kappaB-dependent manner and a NF-AT-d ependent manner, deletion of this element from the LTR did not affect the H Bx-mediated up-regulation in the presence of Tat and/or mitogens. In contra st, mutation of the proximal LTR Sp1-binding sites abolished the HBx-mediat ed synergistic activation, but only when it was accompanied by deletion of the kappaB enhancer. When HBx was targeted to the nucleus, its ability to s ynergize with cellular activation stimuli was maintained. Furthermore, muta tions of HBx affecting its interaction with the basal transcription machine ry abrogated the synergistic activation by HBx, suggesting that this protei n exerts its function by acting as a nuclear co-activator. These results in dicate that HBx could contribute to a faster progression to AIDS in HBV-HIV co-infected individuals.