Transcriptome analysis of HIV-infected peripheral blood monocytes: Gene transcripts and networks associated with neurocognitive functioning

- This study used standard differential gene expression analysis and WGCNA.
- Expression of several genes was associated with neurocognitive functioning.
- Two biological processes were associated with neurocognitive functioning.
- No associations were found with HAND diagnosis, CD4, viral load, or substance use.

Immunologic dysfunction, mediated via monocyte activity, has been implicated in the development of HIV-associated neurocognitive disorder (HAND). We hypothesized that transcriptome changes in peripheral blood monocytes relate to neurocognitive functioning in HIV+ individuals, and that such alterations could be useful as biomarkers of worsening HAND.MethodsmRNA was isolated from the monocytes of 86 HIV + adults and analyzed with the Illumina HT-12 v4 Expression BeadChip. Neurocognitive functioning, HAND diagnosis, and other clinical and virologic variables were determined. Data were analyzed using standard expression analysis and weighted gene co-expression network analysis (WGCNA).ResultsNeurocognitive functioning was correlated with multiple gene transcripts in the standard expression analysis. WGCNA identified two nominally significant co-expression modules associated with neurocognitive functioning, which were enriched with genes involved in mitotic processes and translational elongation.ConclusionsMultiple modified gene transcripts involved in inflammation, cytoprotection, and neurodegeneration were correlated with neurocognitive functioning. The associations were not strong enough to justify their use as biomarkers of HAND; however, the associations of two co-expression modules with neurocognitive functioning warrant further exploration.