Journal
ANTIVIRAL RESEARCH
Volume 71, Issue 2-3, Pages 301-306Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2006.01.002
Keywords
HIV-1; chemotherapy; transcription; Tat; NF-kappa B
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Human immiunodeficiency virus type 1 (HIV-1) gene expression and transcription is a crucial step in the viral replication cycle, which is considered to be a potential target for inhibition of HIV-1. Among the factors involved in this step, the cellular protein nuclear factor (NF)-kappa B is the most powerful inducer of HIV-1 gene expression. On the other hand, the viral protein Tat plays a central role in sustaining a high level of HIV-1 replication. Several compounds have been reported to selectively inhibit the functions of Tat and NF-kappa B. Tat inhibitors target either the Tat/TAR RNA interaction or the Tat cofactor cyclin-dependent kinase 9/cyclin T I. Antioxidants, protein kinase C inhibitors, and I kappa B kinase inhibitors are known to suppress the activation of NF-kappa B. Although some of the compounds inhibit HIV-1 replication in cell cultures at low concentrations, they also have considerable toxicity to the host cells. Considering the increase of treatment failure cases in highly active antiretroviral therapy due to the emergence of multidrug resistance, HIV-1 gene expression inhibitors should be extensively studied as alternative approach to effective anti-HIV-1 chemotherapy. (c) 2006 Elsevier B.V. All rights reserved.
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