Activation of HIV-1 transcription by Tat in cells derived from the CNS: evidence for the participation of NF-kappa B--a review.
Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immune deficiency syndrome (AIDS). The Tat protein of HIV-1 is a potent activator of transcription directed by the viral long terminal repeat. It has been widely reported that this activation requires a specific interaction between Tat and a RNA target termed TAR in the 5'-leader sequence of HIV-1 mRNAs. In this report we present data and describe results which illustrate that under appropriate conditions activation of transcription by Tat occurs independent of the TAR element. The ability to mediate TAR-independent transactivation by Tat is constitutive in some central nervous system cells and requires prior activation in others such as T lymphocytes. Evidence implicating a specific transcription factor in mediating Tat activation is also presented. Studies with site-directed mutants demonstrate that the RNA-binding domain of Tat is dispensable for TAR-independent activation of HIV-1. In contrast, the requirement for specific components of the Tat activation domain suggests that common targets exist for this viral activation factor to exert its activity in TAR-independent and TAR-dependent transactivation pathways of HIV-1 transcriptional activation. A working model of TAR-independent transactivation, which we believe may be responsible for the activation of cellular genes which contribute to AIDS pathology, is presented.
Taylor
J P
JP
Molecular Neurovirology Section, Jefferson Institute of Molecular Medicine, Philadelphia, PA.
Khalili
K
K
D001483:Base Sequence; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000502:physiology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D046911:Macromolecular Substances; D008954:Models, Biological; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D046911:Macromolecular Substances; D016328:NF-kappa B; D012333:RNA, Messenger; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus