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

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• 作者：Andrew J. Levine ; Steve Horvath ; Eric N. Miller ; Elyse J. Singer ; Paul Shapshak ; Gayle C. Baldwin ; Otoniel Mart铆nez-Maza ; Mallory D. Witt ; Peter Langfelder
• 关键词：HIV-associated neurocognitive disorder ; transcriptome ; Monocyte ; IL6R ; gene expression ; WGCNA
• 刊名：Journal of Neuroimmunology
• 出版年：15 December, 2013
• 年：2013
• 卷：265
• 期：1-2
• 页码：96-105
• 全文大小：1101 K

文摘

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

<p>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

<p>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

<p>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.