R5 and X4 HIV Viruses Differentially Modulate Host Gene Expression in Resting CD4 + T Cells

Abstract

During HIV-1 infection, distinct biological phenotypes are observed between R5 and X4 HIV-1 strains with respect to pathogenicity and tropism. In this study, temporal changes of the expression levels of the complete human transcriptome, representing 47,000 well-characterized human transcripts, were monitored in the first 24 h during HIV-1 R5 and X4 exposition in resting primary CD4⁺ T cells. We provide evidence that R5 viruses modulate, to a greater extent than X4 viruses, the level of mRNA of the resting CD4⁺ T cells. Indeed, modulation of the TCR signaling and the actin organization involving the WAVE/ABI complex and the ARP2/3 complex appeared to be associated with R5 exposition. The data suggest that the ability of R5 viruses to modulate TCR-mediated actin polymerization and signaling creates a favorable environment for CD4⁺ T cell activation after TCR stimulation and may partly explain why R5 is the primary strain observed early in the natural infection process.