Entry coreceptor use and fusion inhibitor T20 sensitivity of dual-tropic R5X4 HIV-1 in primary macrophage infection

Journal of Acquired Immune Deficiency Syndromes : JAIDS
Yanjie YiRonald G Collman

Abstract

Macrophages are important targets for HIV-1, and R5X4 strains play a central role in pathogenesis, especially in late-stage patients who may receive the fusion inhibitor T20 (enfuvirtide). Sensitivity to T20 varies markedly among HIV-1 strains and is influenced by viral and cellular factors that affect Env/CD4/coreceptor interactions. We addressed the relation between T20 inhibition and the pathway by which R5X4 HIV-1 infects primary macrophages, which express both coreceptors. In U87/CD4/coreceptor cells, T20 sensitivity for entry through CCR5 and CXCR4 was correlated. In macrophages, the proportion of total entry mediated by each coreceptor differed among isolates. Neither pathway was uniformly more or less sensitive to T20, however, nor did the proportion of entry mediated by each coreceptor predict T20 sensitivity. T20 sensitivity for macrophage infection overall correlated modestly with that for entry through CCR5 but not through CXCR4; however, unlike U87 cells, sensitivity of entry through CCR5 and CXCR4 was not correlated. These results suggest that strain-specific factors influence R5X4 T20 sensitivity regardless of the coreceptor used, an absence of systematic differences in efficiency by which R5X4 strains use the 2 ...Continue Reading

References

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Citations

Jul 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ronald S VeazeyJohn P Moore
Sep 2, 2009·Antimicrobial Agents and Chemotherapy·Louis AlexanderPin-Fang Lin
Feb 10, 2011·Journal of Translational Medicine·Lamorris M LoftinRonald G Collman
Nov 29, 2011·Fundamental & Clinical Pharmacology·Palanee Ammaranond, Sayompoo Sanguansittianan
Oct 22, 2009·Antiviral Chemistry & Chemotherapy·Christina Gavegnano, Raymond F Schinazi
Jan 1, 2014·Molecular and Cellular Therapies·Amit Kumar, Georges Herbein

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