TABLE 2.
Top Predicted Networks Altered Based on Transcriptomic Changes. * No canonical pathways altered but genes significantly altered were characteristically expressed on microvascular endothelial cells, and perivascular cells. # Study specifically looked at ion channel-related genes. @ GAzar software was used to identify top GO pathways affected. AD, Alzheimer’s Disease; MS, Multiple Sclerosis; ART, antiretroviral therapy. $ IPA was used to predict top canonical pathways altered. & Gene categories designated by authors, no directionality was provided. *Genes altered were correlated with NCI. to identify common impairment genes. Common genes used for enrichment analysis.
| Study | Groups included in the study | Networks upregulated | Networks downregulated |
|---|---|---|---|
| Masliah et al. (2004) | HIV+ with HIVE vs. HIV+ no HIVE | Interferon/antiviral response, neuroinflammation, cell cycle, transcription, signaling, cytoskeletal proteins, cell adhesion/extracellular matrix | Signaling, neuronal, ion transport, cell cycle, transcriptional regulators, cytoskeletal proteins, cell adhesion/extracellular matrix |
| Gelman et al. (2004) | HIV− vs. HIV+ with HAD or MCMD or NPI-O | Ion transport# | Ion transport# |
| Shapshak et al. (2004) | HIV+ incl. HIVE and/or HAD vs. HIV—/Ctl | Signaling, splicing, cell cycle, NMDA receptor signaling, synapse, protein tags, ribosomal proteins, transcription, senescence, proteasome, cytoskeleton, ion transport, mitochondrial translation& | |
| Everall et al. (2005) | HIV+ no HIVE vs. HIV+ HIVE vs. HIV+ HIVE plus METH | Signaling, ion transport, interferon/antiviral response, cell adhesion/extracellular matrix, neuroinflammation, cell cycle, transcription, cytoskeletal proteins | Signaling, ion transport, neuronal, cell adhesion/extracellular matrix, DNA repair, cell cycle, transcription, cytoskeletal proteins |
| Borjabad et al. (2011) | HIV- vs. untreated HAND with and without HIVE | Immune response, antigen presentation, endogenous antigen, antigen processing, endogenous antigen via MHC class I, inflammatory response, response to virus, antigen presentation, exogenous antigen, antigen processing, exogenous antigen via MHC class II, complement activation, classical pathway@ | Synaptic transmission, neurogenesis, homophilic cell adhesion, potassium ion transport, oxygen transport, ion transport, cation transport, sodium ion transport@ |
| Untreated HAND vs. cART treated HAND | Immune response, interferon response, regulation of cell cycle | Myelin-related, microtubule-based movement, regulation of cell cycle | |
| Borjabad and Volsky, (2012) | HAND from groups in five HIV studies Masliah et al. (2004); Gelman et al. (2004); Shapshak et al. (2004); Everall et al. (2005); Borjabad et al. (2011) vs. 18 AD | Immune response, defense response, response to biotic stimulus, response to external stimulus, antigen presentation | Transmission of nerve impulse, synaptic transmission, transport, cell-cell signaling, synaptic vesicle |
| ART-HAND from groups in five HIV studies vs. 18 AD | Immune response, defense response, antigen processing, antigen presentation, signal transducer activity | DNA helicase activity, hydrolase activity, cell growth and/or maintenance, binding | |
| HAND from groups in five HIV studies vs. nine MS studies | Immune response, defense response, response to biotic stimulus, response to external stimulus, response stress | Calmodulin-dependent protein kinase I activity, non-kinase phorbol ester receptor activity, calcium/calmodulin-dependent kinase activity, phorbol ester receptor activity | |
| ART-HAND from groups in five HIV studies vs. nine MS studies | Immune response, defense response, antigen processing, response to biotic stimulus, response to external stimulus | Intracellular signaling cascade, signal transduction, catalytic activity, cell communication, cellular process | |
| Gelman et al. (2012) | HIV−/Ctl vs. HIV+/CN with no HIVE | — | G-coupled receptor signaling, cyclic AMP-mediated signaling$ |
| HIV−/Ctl vs. HIV+ with NCI and no HIVE | — | Alterations in brain microvascular endothelial cells, and perivascular cells* | |
| HIV−/Ctl vs. HIV+ with NCI and HIVE | Interferon/antiviral response, activation of IRF cytosolic pattern recognition receptor, antigen presentation, pattern recognition receptors for bacteria and viruses, complement system, acute phase response signaling, hepatic fibrosis, toll-like receptor signaling, protein ubiquitination pathway, caveolar mediated endocytosis, liver X receptor$ | GABA receptor signaling, clathrin mediated endocytosis, glutamate receptor signaling, 14-3-3 mediated signaling, synaptic long-term potentiation, cyclic AMP-mediated signaling, calcium signaling, axonal guidance signaling, chemokine signaling, ephrin receptor signaling, oxidative phosphorylation$ | |
| Zhou et al. (2012) | HIV+ HAD vs. HIV+ no dementia | Dendrite, ATPase activity coupled to transmembrane movement of ions, ATPase activity coupled to transmembrane movement of ions phosphorylation mechanism, regulation of blood pressure, protein homo oligomerization, mRNA binding, feeding behavior, and cytoskeleton dependent intracellular transport | |
| Levine et al. (2013) | HIV+ with HAD and HIVE vs. HIV+ with HAD, no HIVE vs. HIV+/CN, no HIVE* | Cortex: Transcription regulation, receptor activity, DNA binding. NCI basal ganglia: protein kinase activity, Homo Sapiens 19 | Cortex: Mitochondrion, mitotic cell cycle, DNA repair, proteasome complex, nucleus |
| White matter: transcription regulation, Homo Sapiens 19, chondroitin/heparin sulfate biosynthesis | |||
| HIV+ with HAD and HIVE, HIV+ with HAD, no HIVE, HIV+/CN, no HIVE vs. HIV−/Ctl vs. AD+ HIV−* | Cell differentiation, activator, repeat, cell communication, regulation of transcription, phosphorylation | Cytoplasm, energy pathways, mitochondrion, tricarboxylic acid cycle, transit peptide, synaptic vesicle | |
| Canchi et al. (2020) | HIV+ with HAD vs. HIV+ with MND vs. HIV+ with ANI vs. HIV+/CN | Immune response, RNA editing | Synaptic maintenance |