Multiple effects of HIV-1 trans-activator protein on the pathogenesis of HIV-1 infection

• Published in: European journal of clinical investigation 2004-01, Vol.34 (1), p.57-66
• Main Authors: Huigen, M. C. D. G., Kamp, W., Nottet, H. S. L. M.
• Format: Article
• Language: English
• Subjects: Acquired immunodeficiency syndrome; Acquired Immunodeficiency Syndrome - genetics; Acquired Immunodeficiency Syndrome - immunology; AIDS Dementia Complex - immunology; AIDS Vaccines - therapeutic use; gene expression; Gene Expression Regulation, Viral - genetics; Gene Products, tat - genetics; Genes, Viral - genetics; HIV Infections - genetics; HIV Infections - immunology; HIV-1 - genetics; HIV-1 trans-activator (Tat) protein; human immunodeficiency virus type 1 (HIV-1); Humans; immune regulation; Immune Tolerance - immunology; Models, Genetic; Sarcoma, Kaposi - immunology; tat Gene Products, Human Immunodeficiency Virus; Trans-Activators - genetics; Transcription, Genetic
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2004.01282.x

The HIV‐1 trans‐activator (Tat) protein is proposed as an important factor in the complex HIV‐induced pathogenesis of AIDS. In this paper, multiple effects of this viral protein are described. Originally discovered as an intracellular activator of HIV‐1 transcription, Tat was found to regulate viral reverse transcription as well. Trans‐activator was found to be secreted by HIV‐infected cells and taken up by neighbouring cells. In this way, Tat is able to affect both infected and uninfected cells. Intracellularly, Tat can deregulate the expression of several heterologous cellular and viral genes. Extracellular Tat can contribute to the spreading of HIV‐1 and immunosuppression of uninfected cells. Finally, there is evidence that exogenous Tat is involved in AIDS‐associated pathologies such as Kaposi's sarcoma and HIV‐associated dementia. These capacities together accelerate the progression towards AIDS and make Tat an interesting candidate as a constituent of an anti‐AIDS vaccine.