HIV latency reversing agents act through Tat post translational modifications
Georges Khoury, Talia M Mota, Shuang Li, Carolin Tumpach, Michelle Y Lee, Jonathan Jacobson, Leigh Harty, Jenny L Anderson, Sharon R Lewin, Damian FJ Purcell
RETROVIROLOGY | BMC | Published : 2018
BACKGROUND: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated additive effects of LRAs with the viral protein Tat in initiating transcription, but less is known about how LRAs interact with Tat, particularly through basic residues that may be post-translationally modified to alter the behaviour of Tat for processive transcription and co-transcriptional RNA processing. RESULTS: Here we show that various lysine and arginine mutations reduce the capacity of Tat to induce both transcription and mRNA splicing. The lysine 28 and lysine 50 resid..View full abstract
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Awarded by NHMRC of Australia
Awarded by National Institutes for Health Delaney AIDS Research Enterprise
This work was supported by project grant APP1129320, and program grant APP1052979 from the NHMRC of Australia. SRL is an NHMRC practitioner fellow and is supported by the National Institutes for Health Delaney AIDS Research Enterprise (DARE U19 AI096109), and the American Foundation for AIDS Research.