PMID: 12788638Jun 6, 2003Paper

Differential activation of Tat variants in mitogen-stimulated cells: implications for HIV-1 postintegration latency

Virology
Syed M RezaTsafi Pe'ery

Abstract

Like other HIV-1 (human immunodeficiency virus type 1) proteins, Tat undergoes rapid mutation and occurs in numerous sequence variants in nature. Virus isolated from patients often has defects in Tat that lower its activity. The levels of P-TEFb, an essential cellular cofactor for Tat, are elevated by T-cell activation. To test the hypothesis that stimulation of P-TEFb levels might compensate for attenuation of Tat activity, we generated Tat constructs with a range of transactivation function. Transactivation by the Tat mutants correlated with their ability to bind to P-TEFb in vitro. Treatment of U937 cells with the phorbol ester PMA (phorbol myristate acetate) induced P-TEFb and stimulated Tat transactivation for alleles with basal transcription activity above a threshold (>5% compared to wild-type). Highly active alleles (>66% of wild-type) were stimulated to a lesser extent than those with activity in the intermediate range. Thus, attenuation of Tat function, in concert with low levels of P-TEFb activity, could serve to keep the virus in a latent state in quiescent cells yet permit viral replication after cell activation.

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Citations

Jan 13, 2012·Journal of Virology·Daniel A DonahueMark A Wainberg
Feb 18, 2003·Molecular and Cellular Biology·Mainul HoqueTsafi Pe'ery
Jul 19, 2011·Journal of Molecular Biology·Mainul HoqueMichael B Mathews
Jan 18, 2005·The Journal of Biological Chemistry·Mainul HoqueTsafi Pe'ery
Mar 6, 2019·Medical Microbiology and Immunology·Cassandra SpectorMichael R Nonnemacher

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