Differential coreceptor expression allows for independent evolution of non–syncytium-inducing and syncytium-inducing HIV-1
Ronald P. van Rij, … , Ana-Maria de Roda Husman, Hanneke Schuitemaker
Ronald P. van Rij, … , Ana-Maria de Roda Husman, Hanneke Schuitemaker
Published October 15, 2000
Citation Information: J Clin Invest. 2000;106(8):1039-1052. https://doi.org/10.1172/JCI7953.
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Article

Differential coreceptor expression allows for independent evolution of non–syncytium-inducing and syncytium-inducing HIV-1

Abstract

We demonstrated previously that CD45RA+ CD4+ T cells are infected primarily by syncytium-inducing (SI) HIV-1 variants, whereas CD45RO+ CD4+ T cells harbor both non-SI (NSI) and SI HIV-1 variants. Here, we studied evolution of tropism for CD45RA+ and CD45RO+ CD4+ cells, coreceptor usage, and molecular phylogeny of coexisting NSI and SI HIV-1 clones that were isolated from four patients in the period spanning SI conversion. NSI variants were CCR5-restricted and could be isolated throughout infection from CD45RO+ CD4+ cells. SI variants seemed to evolve in CD45RO+ CD4+ cells, but, in time, SI HIV-1 infection of CD45RA+ CD4+ cells equaled infection of CD45RO+ CD4+ cells. In parallel with this shift, SI HIV-1 variants first used both coreceptors CCR5 and CXCR4, but eventually lost the ability to use CCR5. Phylogenetically, NSI and SI HIV-1 populations diverged over time. We observed a differential expression of HIV-1 coreceptors within CD45RA+ and CD45RO+ cells, which allowed us to isolate virus from purified CCR5+ CXCR4– and CCR5– CXCR4+ CD4+ cells. The CCR5+ subset was exclusively infected by CCR5-dependent HIV-1 clones, whereas SI clones were preferentially isolated from the CXCR4+ subset. The differential expression of HIV-1 coreceptors provides distinct cellular niches for NSI and SI HIV-1, contributing to their coexistence and independent evolutionary pathways.

Authors

Ronald P. van Rij, Hetty Blaak, Janny A. Visser, Margreet Brouwer, Ronald Rientsma, Silvia Broersen, Ana-Maria de Roda Husman, Hanneke Schuitemaker

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Longitudinal analysis of coreceptor usage of NSI and SI HIV-1 clones. Ba...
Longitudinal analysis of coreceptor usage of NSI and SI HIV-1 clones. Based on the ability to infect MT2 cells, viral clones were subdivided in NSI (left panels) and in SI (right panels) phenotypes. Coreceptor usage was tested by the ability to productively infect U87 cells transfected with CD4 and one of the HIV-1 coreceptors CCR3, CCR5, or CXCR4 after cell-free infection of these cells. Bars indicate in vitro specificity for HIV-1 coreceptors: CCR5 (R5), open bars; CCR5 and CXCR4 (R5X4), gray bars; CCR3, CCR5, and CXCR4 (R3R5X4), light gray bars; CCR3 and CXCR4 (R3X4), dark gray bars; and CXCR4 (X4), filled bars.