Transcriptome analysis of primary monocytes shows global down-regulation of genetic networks in HIV viremic patients versus long-term non-progressors

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Abstract

Despite significant contributions of monocytes to HIV persistence, the genomic basis of HIV-infection of monocytes and its association with plasma viremia remain elusive. To understand HIV interactions with monocytes during disease progression, monocytic transcriptomes from long-term non-progressors (LTNP), HIV+ patients with viral load <1000, with viral load>1000, and seronegative controls were analyzed using Illumina microarray. Differentially expressed genes were identified (fold change >2; adjusted p<0.05) and GSEA between HIV+ groups demonstrated that the down-regulation of the pathways including Toll-like receptor (TLR) signaling, cytokine-cytokine receptor interaction, cell cycle and apoptosis was significantly associated with the viremic groups, whereas their up-regulation with the LTNP group. The down-regulation of TLR pathway in the viremic patients was exemplified by the decreased expression of TLR with the subsequent tuning down of MAPK, NF-κB, JAK-STAT, and IRF cascades. These data provide the first transcriptomic distinction between HIV+ progressors and LTNPs based on primary monocytes. © 2012.

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Wu, J. Q., Ruth Sassé, T., Wolkenstein, G., Conceicao, V., Miranda Saksena, M., Soedjono, M., … Saksena, N. K. (2013). Transcriptome analysis of primary monocytes shows global down-regulation of genetic networks in HIV viremic patients versus long-term non-progressors. Virology, 435(2), 308–319. https://doi.org/10.1016/j.virol.2012.10.026

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