Will Diverse Tat Interactions Lead to Novel Antiretroviral Drug Targets?
David Harrich, Nigel McMillan, Liliana Munoz, Ann Apolloni and Luke Meredith
Affiliation: HIV-1 Molecular Virology Laboratory, Division of Immunology and Infectious Diseases, Queensland Institute of Medical Research, Royal Brisbane Hospital Post Office, Brisbane 4029, Qld, Australia.
More than fifteen years following the description of Tat as a critical HIV gene expression regulatory protein, additional roles for Tat in HIV replication have been described, including reverse transcription. Tat achieves function through direct interaction with viral proteins, including reverse transcriptase, and numerous cellular proteins including cyclin T1, RNA polymerase II, protein kinase R (PKR), p300/CBP, and P/CAF. Despite our advanced knowledge of how Tat operates, this has not yet resulted in the discovery of effective agents capable of targeting various Tat functions. Nevertheless, Tat remains an attractive, virus-specific molecule and detailed understanding of specific protein interaction holds promise for future drug discovery.
Keywords: HIV-1, Tat, transcription, reverse transcription, trans-activation, acetylation, methylation, phosphorylation
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