The hepatitis B virus X protein induces HIV-1 replication and transcription in synergy with T-cell activation signals: functional roles of NF-kappaB/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-infection on the clinical outcome of HIV infection has not been elucidated. We herein demonstrate that the HBV X protein (HBx) superinduces ongoing HIV-1 replication and HIV-1 long terminal repeat (LTR) transcription by synergizing with Tat protein and with T-cell activation signals. Although HBx cooperated with mitogenic stimuli in the induction of reporter plasmids harboring the HIV-1 kappaB enhancer, in both a NF-kappaB-dependent manner and a NF-AT-dependent manner, deletion of this element from the LTR did not affect the HBx-mediated up-regulation in the presence of Tat and/or mitogens. In contrast, mutation of the proximal LTR Sp1-binding sites abolished the HBx-mediated synergistic activation, but only when it was accompanied by deletion of the kappaB enhancer. When HBx was targeted to the nucleus, its ability to synergize with cellular activation stimuli was maintained. Furthermore, mutations of HBx affecting its interaction with the basal transcription machinery abrogated the synergistic activation by HBx, suggesting that this protein exerts its function by acting as a nuclear co-activator. These results indicate that HBx could contribute to a faster progression to AIDS in HBV-HIV co-infected individuals.
Gómez-Gonzalo
M
M
Unidad de Biologia Molecular, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Carretero
M
M
Rullas
J
J
Lara-Pezzi
E
E
Aramburu
J
J
Berkhout
B
B
Alcamí
J
J
López-Cabrera
M
M
D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004742:Enhancer Elements, Genetic; D015696:Gene Products, tat / Q000502:physiology; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication / Q000502:physiology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D054322:tat Gene Products, Human Immunodeficiency Virus