Highlights
- •Microglia activation play a key role in progression of HIV-associated Neurocognitive Disorder (HAND).
- •Deconvolution method represents a new approach to define the brain cells' architecture HAND.
- •OAS3 is a 2′-5′-oligoadenylate synthetases high modulated in HIV infection.
- •In HAND/HIVE brains the high expression levels of OAS3 were associated with an inflammatory profile.
- •Neuronal activation profile is significantly activated in HAND patients with low OAS3 expression.
Abstract
Neurological complications of AIDS (NeuroAIDS) include primary HIV-associated neurocognitive
disorder (HAND). OAS3 is an enzyme belonging to the 2′, 5′ oligoadenylate synthase
family induced by type I interferons and involved in the degradation of both viral
and endogenous RNA. Here, we used microarray datasets from NCBI of brain samples of
non-demented HIV-negative controls (NDC), HIV, deceased patients with HAND and encephalitis
(HIVE) (treated and untreated with antiretroviral therapy, ART), and with HAND without
HIVE. The HAND/HIVE patients were stratified according to the OAS3 gene expression.
The genes positively and negatively correlated to the OAS3 gene expression were used
to perform a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging
to sixteen signatures. Expression analysis revealed significantly higher OAS3 expression
in HAND/HIVE and HAND/HIVE/ART compared with NDC. OAS3 expressed an excellent diagnostic
ability to discriminate NDC from HAND/HIVE, HAND from HAND/HIVE, HAND from HAND/HIVE/ART,
and HIV from HAND/HIVE. Noteworthy, OAS3 expression levels in the brains of HAND/HIVE
patients were positively correlated with viral load in both peripheral blood and cerebrospinal
fluid (CSF). Furthermore, deconvolution analysis revealed that the genes positively
correlated to OAS3 expression were associated with inflammatory signatures. Neuronal
activation profiles were significantly activated by the genes negatively correlated
to OAS3 expression levels. Moreover, gene ontology analysis performed on genes characterizing
the microglia signature highlighted an immune response as a main biological process.
According to our results, genes positively correlated to OAS3 gene expression in the
brains of HAND/HIVE patients are associated with inflammatory transcriptomic signatures
and likely worse cognitive impairment.
Keywords
Abbreviations:
MD (microarray datasets), MeV (MultiExperiment Viewer), FDR (false discovery rate), CNS (central nervous system), NDC (non-demented HIV-negative controls), GSPC (genes significant positive correlated), GSNC (genes significant negative correlated), SDEG (Significantly Different Expressed Genes), AUC (area under the ROC curve), GSPC-OAS3 (genes significantly positively correlated to OAS3), GSNC-OAS3 (genes significantly negatively correlated to OAS3), HAND (HIV-associated neurocognitive disorder), ANI (asymptomatic neurocognitive impairment), MND (mild neurocognitive disorder), HAD (HIV associated dementia), ART (antiretroviral therapy), CSF (Cerebrospinal fluid), HIVE (HIV encephalitis)To read this article in full you will need to make a payment
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References
- Does the informal caregiver notice HIV associated mild cognitive impairment in people living with HIV?.AIDS Care. 2016; 28: 221-227
- HIV-associated neurocognitive disorder.Lancet Infect. Dis. 2013; 13: 976-986
- Updated research nosology for HIV-associated neurocognitive disorders.Neurology. 2007; 69: 1789-1799
- Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia.Brain Res. 2000; 853: 236-244
- Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy.J. Neuro-Oncol. 2009; 15: 360-370
- A new possible mechanism of human immunodeficiency virus type 1 infection of neural cells.Neurobiol. Dis. 2002; 11: 469-478
- HIV-1 infection of neurons might account for progressive HIV-1-associated encephalopathy in children.J. Mol. Neurosci. 2005; 27: 79-89
- ATP mediates rapid microglial response to local brain injury in vivo.Nat. Neurosci. 2005; 8: 752-758
- Risk factors and pathogenesis of HIV-associated neurocognitive disorder: the role of host genetics.Int. J. Mol. Sci. 2018; 19
- The role of HIV infection in neurologic injury.Brain Sci. 2017; 7
- Imaging correlates of the blood-brain barrier disruption in HIV-associated neurocognitive disorder and therapeutic implications.AIDS. 2019; 33: 1843-1852
- Induction of OAS gene family in HIV monocyte infected patients with high and low viral load.Antivir. Res. 2016; 131: 66-73
- OAS gene family expression is associated with HIV-related neurocognitive disorders.Mol. Neurobiol. 2018; 55: 1905-1914
- Nuclear import sequence identification in hOAS3 protein.Inflamm. Res. 2016; 65: 895-904
- Structural mechanism of sensing long dsRNA via a noncatalytic domain in human oligoadenylate synthetase 3.Proc. Natl. Acad. Sci. U. S. A. 2015; 112: 3949-3954
- Prognostic characterization of OAS1/OAS2/OAS3/OASL in breast cancer.BMC Cancer. 2020; 20: 575
- The gene expression omnibus database.Methods Mol. Biol. 2016; 1418: 93-110
- Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders.PLoS Pathog. 2011; 7e1002213
- National Neuro, the National NeuroAIDS tissue consortium brain gene array: two types of HIV-associated neurocognitive impairment.PLoS One. 2012; 7e46178
- Fasting and fast food diet play an opposite role in mice brain aging.Mol. Neurobiol. 2018; 55: 6881-6893
- Middle-aged healthy women and Alzheimer's disease patients present an overlapping of brain cell transcriptional profile.Neuroscience. 2019; 406: 333-344
- False discovery rate control incorporating phylogenetic tree increases detection power in microbiome-wide multiple testing.Bioinformatics. 2017; 33: 2873-2881
- Linear models and empirical bayes methods for assessing differential expression in microarray experiments.Stat Appl Genet Mol Biol. 2004; 3 (Article3)
- GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor.Bioinformatics. 2007; 23: 1846-1847
- STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets.Nucleic Acids Res. 2019; 47: D607-D613
- Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer's disease.Genome Med. 2016; 8: 104
- Lipopolysaccharide activates Toll-like receptor 4 (TLR4)-mediated NF-kappaB signaling pathway and proinflammatory response in human pericytes.J. Biol. Chem. 2014; 289: 2457-2468
- Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data.Genes Immun. 2005; 6: 319-331
- Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.Nature Genetics. 2000; 25: 25-29
- Expansion of the Gene Ontology knowledgebase and resources.Nucleic Acids Res. 2017; 45: D331-D338
- Transcriptomic comparison of human and mouse brain microvessels.Sci. Rep. 2020; 10: 12358
- KEGG: Kyoto encyclopedia of genes and genomes.Nucleic Acids Res. 2000; 28: 27-30
- Toward understanding the origin and evolution of cellular organisms.Protein Sci. 2019; 28: 1947-1951
- KEGG: integrating viruses and cellular organisms.Nucleic Acids Res. 2021; 49: D545-D551
- Transcriptional profile of aging in C. elegans.Curr. Biol. 2002; 12: 1566-1573
- A transcriptional profile of aging in the human kidney.PLoS Biol. 2004; 2e427
- Bayesian Inference in Statistical Analysis. 1992
- Analysis of microarray data using Z score transformation.J Mol Diagn. 2003; 5: 73-81
- A microarray platform-independent classification tool for cell of origin class allows comparative analysis of gene expression in diffuse large B-cell lymphoma.PLoS One. 2013; 8e55895
- Differences in gene expression between B-cell chronic lymphocytic leukemia and normal B cells: a meta-analysis of three microarray studies.Bioinformatics. 2004; 20: 3166-3178
- TB database: an integrated platform for tuberculosis research.Nucleic Acids Res. 2009; 37: D499-D508
- YuGene: a simple approach to scale gene expression data derived from different platforms for integrated analyses.Genomics. 2014; 103: 239-251
- An integrated cross-platform prognosis study on neuroblastoma patients.Genomics. 2008; 92: 195-203
- Can survival prediction be improved by merging gene expression data sets?.PLoS One. 2009; 4e7431
- Clustering by fast search and merge of local density peaks for gene expression microarray data.Sci. Rep. 2017; 7: 45602
- Application of z-score transformation to Affymetrix data.Appl. Bioinforma. 2003; 2: 209-217
- Expression of Bcl-2 is a favorable prognostic biomarker in lung squamous cell carcinoma.Oncol. Lett. 2018; 15: 6925-6930
- Feature selection and tumor classification for microarray data using relaxed Lasso and generalized multi-class support vector machine.J. Theor. Biol. 2019; 463: 77-91
- Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep.PLoS One. 2019; 14e0226697
- The expression levels of CHI3L1 and IL15Ralpha correlate with TGM2 in duodenum biopsies of patients with celiac disease.Inflammation Research. 2020; 69: 925-935
- The chitinases expression is related to Simian Immunodeficiency Virus Encephalitis (SIVE) and in HIV encephalitis (HIVE).Virus Res. 2017; 227: 220-230
- Chitinase expression in Alzheimer’s disease and non-demented brains regions.J. Neurol. Sci. 2016; 369: 242-249
- Immunoproteasome genes are modulated in CD34(+) JAK2(V617F) mutated cells from primary myelofibrosis patients.Int. J. Mol. Sci. 2020; 21
- Different pediatric brain tumors are associated with different gene expression profiling.Acta Histochem. 2015; 117: 477-485
- Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action.Cell. 1993; 72: 753-765
- Type I IFN--a blunt spear in fighting HIV-1 infection.Cytokine Growth Factor Rev. 2015; 26: 143-158
- Interferons and HIV infection: the good, the bad, and the ugly.Pathog Immun. 2016; 1: 107-116
- Immune responses to RNA-virus infections of the CNS.Nat Rev Immunol. 2003; 3: 493-502
- Microbial molecule ingress promotes neuroinflammation and brain CCR5 expression in persons with HIV-associated neurocognitive disorders.Brain Behav. Immun. 2023; 107: 110-123
- Characterization of macrophage-tropic HIV-1 infection of central nervous system cells and the influence of inflammation.J. Virol. 2022; 96e0095722
- Differential effects of integrase strand transfer inhibitors, elvitegravir and raltegravir, on oligodendrocyte maturation: A role for the integrated stress response.Glia. 2021; 69: 362-376
- HIV-1 gp120 and tobacco smoke synergistically disrupt the integrity of the blood-brain barrier.Eur. J. Cell Biol. 2022; 101151271
- Changing patterns in the neuropathogenesis of HIV during the HAART era.Brain Pathol. 2003; 13: 195-210
- HIV-1-infected astrocytes and the microglial proteome.J. NeuroImmune Pharmacol. 2008; 3: 173-186
- Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis.Ann. Med. 2021; 53: 43-69
Article info
Publication history
Published online: January 19, 2023
Accepted:
January 16,
2023
Received in revised form:
January 10,
2023
Received:
August 13,
2022
Identification
Copyright
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