Abstract
The human immunodeficiency virus type 1 (HIV-1) promoter or long-terminal repeat (LTR) regulates viral gene expression by interacting with multiple viral and host factors. The viral transactivator protein Tat plays an important role in transcriptional activation of HIV-1 gene expression. Functional domains of Tat and its interaction with transactivation response element RNA and cellular transcription factors have been examined. Genetic variation within tat of different HIV-1 subtypes has been shown to affect the interaction of the viral transactivator with cellular and/or viral proteins, influencing the overall level of transcriptional activation as well as its action as a neurotoxic protein. Consequently, the genetic variability within tat may impact the molecular architecture of functional domains of the Tat protein that may impact HIV pathogenesis and disease. Tat as a therapeutic target for anti-HIV drugs has also been discussed.
Highlights
The human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome (AIDS)
The HIV-1 genome is about 9.8 kb in length, including two viral long-terminal repeats (LTRs) located at both ends when integrated into the host genome
The HIV-1 LTRs are generated during the process of reverse transcription and located on each end of the proviral DNA when the provirus is integrated into the host genome
Summary
The human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV-1 genome is about 9.8 kb in length, including two viral long-terminal repeats (LTRs) located at both ends when integrated into the host genome. The HIV-1 transactivator of transcription (Tat) protein is an early regulatory protein containing from 86 to 106 amino acids in length with a molecular weight of approximately 14 to 16 kDa. Tat is a multifunctional protein that has been proposed to contribute to several pathological consequences of HIV-1 infection. Tat plays an important role in viral transcription and replication, it is capable of inducing the expression of a variety of cellular genes as well as acting as a neurotoxic protein. Because of its pivotal role in viral replication and disease pathogenesis, Tat and the cellular pathways targeted by Tat could be potential targets for new anti-HIV drugs. Therapeutic strategies that have focused on this topic are reviewed
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