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. 2022 Oct 12;12(10):1378.
doi: 10.3390/brainsci12101378.

Gene Co-Expression Network Modular Analysis Reveals Altered Immune Mechanisms in HIV-HAND

Maria Cristina Petralia  1 , Ferdinando Nicoletti  2 , Lyubka Tancheva  3 , Reni Kalfin  3   4 , Paolo Fagone  2 , Katia Mangano  2
Affiliations

Gene Co-Expression Network Modular Analysis Reveals Altered Immune Mechanisms in HIV-HAND

Maria Cristina Petralia et al. Brain Sci. .

Abstract

Although the introduction of HAART has completely changed the natural course of HIV infection, the number of chronic forms of HIV-associated neurocognitive disorder (HAND) has risen. It is estimated that up to half of subjects undergoing HAART therapy exhibit mild cognitive impairments. In the current study, we apply the gene co-expression network modular analysis, a well-established system biology approach, to the gene expression profiles of cases from the National NeuroAIDS Tissue Consortium (NNTC). We observed a negative enrichment for genes associated with the control of immune responses and putatively regulated by the transcription factors IRF8 and SPI1 and by both type I and II interferons. Our study provides evidence of altered immune responses, which are likely associated with the occurrence of HAND in the absence of HIV encephalitis (HIVE).

Keywords: HIV; HIV-HAD; HIV-HAND; HIVE neurocognitive impairment; National NeuroAIDS Tissue Consortium; immune response.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Gene co-expression network modular analysis. Modules enriched by the co-expression network modular analysis of the GSE35864 dataset. The heatmap is color- and size-coded based on the NES (normalized enrichment score) and statistical significance.
Figure 2
Figure 2
Gene co-expression network modular analysis. PPI network for each of the modules identified in the co-Expression network modular analysis of the GSE35864 dataset. Hub genes are indicated in red.
Figure 3
Figure 3
Gene co-expression network modular analysis. Over-representation analysis for the brain cell populations in each of the modules identified in the co-expression network modular analysis of the GSE35864 dataset.
Figure 4
Figure 4
Biological interpretation of the gene co-expression modules obtained from the analysis of the GSE35864 dataset.
Figure 5
Figure 5
Biological interpretation of Module 7. Over-representation analysis (ORA) for the genes belonging to Module 7, performed using the KEGG database.
Figure 6
Figure 6
Biological interpretation of Module 7. GSEA analysis for the genes belonging to Module 7 performed using the KEGG database. The significant pathways are shown.
Figure 7
Figure 7
Regulation of Module 7 genes. (A) Putative transcription factors involved in the regulation of the expression of the genes belonging to Module 7, (B) ligand perturbation analysis showing the factor able to upregulate the expression of the genes belonging to Module 7, (C) ligand perturbation analysis showing the factor able to downregulate the expression of the genes belonging to Module 7.
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