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

TitleTranscriptome analysis of HIV-infected peripheral blood monocytes: gene transcripts and networks associated with neurocognitive functioning
Publication TypeJournal Article
Year of Publication2013
AuthorsLevine, AJ, Horvath, S, Miller, EN, Singer, EJ, Shapshak, P, Baldwin, GC, Martínez-Maza, O, Witt, MD, Langfelder, P
JournalJournal of Neuroimmunology
Volume265
Issue1-2
Pagination96-105
Date Published12/2013
KeywordsExternal, Gene Expression, HIV-associated neurocognitive disorder, IL6R, Monocyte, transcriptome, WGCNA
Abstract

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.  METHODS: mRNA 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).  RESULTS: Neurocognitive 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.  CONCLUSIONS: Multiple 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.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/24094461
DOI10.1016/j.jneuroim.2013.09.016