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106 Targeting CCR5 Density for Treatment and Prevention

Redfield Robert
JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2012
doi: 10.1097/01.qai.0000413783.28964.79

HIV exploits key host cell pathways to complete its viral life cycle. As such, specific host cell pathways could serve as potential therapeutic targets. CCR5 receptor density is a key factor in terms of ability to infect target cells. CCR5 receptor density increases with cell activation and is also associated with replication kinetics. We recently postulated and confirmed that cytostatic agents that induced prolongation of G1-S transition were associated with down regulation of CCR5 expression and that this resulted in enhanced potency of both CCR5 antagonist and fusion entry inhibitors. In addition, we demonstrated that this effect also enhanced the potency of antibodies which block viral entry. The potency of all tested entry inhibitors was directly related to CCR5 density. Prototype CCR5 resistant R5 viruses demonstrated wild type susceptibility when tested in cells with reduced but physiologic CCR5 density. These data suggest that targeting CCR5 density could have therapeutic implications in enhancing potency of HIV entry inhibitors.

© 2012 Lippincott Williams & Wilkins, Inc.