TABLE 3.
Epigenetics Studies. List of studies performed using postmortem brain tissues or blood-derived cells of HIV-infected and uninfected individuals and specific cell types. AD, Alzheimer’s Disease; DTI, diffusion tensor imaging (neuroimaging); HIV−/Ctl, uninfected, healthy control; HIVE, HIVE encephalitis; HAND, HIV associated neurocognitive disorders; NCI, Neurocognitive impairment; HAD, HIV-associated dementia; HIV+/CN, HIV+ cognitive normal subjects; NPI-O, neuropsychologically impaired but not definitely caused by HIV infection due to comorbid factor; MCMD, minor cognitive and motor disorder; MND, Mild neurocognitive disorder; MDD, major depressive disorder; METH, methamphetamine; MRI, magnetic resonance imaging (neuroimaging); NHP, non-human primate; qRT-PCR, quantitative reverse transcription polymerase chain reaction.
| Study (References) | Groups included in the study (number of cases) | Area(s) of the brain | Method | Notes, or miR/target |
|---|---|---|---|---|
| In vitro cultures | ||||
| Eletto et al. (2008) | In vitro, HIV Tat vs. untreated | Primary rat cortical neuronal cell cultures | miRNA microarray | miR-128a/SNAP25 |
| Mukerjee et al. (2011) | In vitro, HIV Vpr vs. untreated | Primary neuronal cell cultures (human) and SHSY-5Y cell line | miR and mRNA Microarray | Multiple miRs/multiple neuronal genes |
| Dave and Khalili (2010) | In vitro, morphine treated vs. untreated, HIV+ vs. uninfected | Human monocyte-derived macrophages | miRNA microarray | 26 miRs/FGF-2, MCP-2, IL-6 |
| Saiyed et al. (2011) | In vitro, HIV Tat vs. untreated with and without siRNA for knockdown of HDAC2 | Primary neuronal cell cultures (human) and SK-N-MC cell line | HDAC knockdown and qRT-PCR | HDAC reduces CREB and CaMKIIa expr |
| Post-mortem brain tissue | ||||
| Yelamanchili et al. (2010) | HIV+ with HAD and HIVE (n = 3) vs. HIV+ no HAD, no HIVE (n = 4) (NHP: SIV+ with SIVE (n = 4) vs. uninfected (n = 4)) | Caudate nucleus (striatum) of HAD and HIVE, and hippo-campus and striatum of SIV+ rhesus monkeys | miRNA microarray, miR qRT-PCR | miR-21/MEF2C |
| Noorbakhsh et al. (2010) | HIV+ with HIVE (n = 4) vs. HIV−/Ctl (n = 4) | Frontal lobe (cortex) | miRNA microarray, qRT-PCR | Multiple miRs/inflammation, immune, cell death genes |
| Tatro et al. (2010) | HIV+ with MDD (n = 5) vs. HIV+ no MDD (n = 5) vs. HIV−/Ctl (n = 3) | Frontal cortex | miR and mRNA Microarray | Multiple miRs/multiple neuronal genes |
| Zhou et al. (2012) | HIV+ with HAD (n = 10) vs. HIV+ no HAD (n = 8) | Frontal cortex | miR Microarray | Multiple miRs/neuronal axon-guidance genes |
| Xu et al. (2017) | HIV+ with HAND and HIVE (n = 10) vs. HIV+ HAND, no HIVE (n = 10) vs. HIV−/Ctl (n = 10) | Midfrontal gyrus (cortex) | miRNA microarray | 17 miRs/genes of peroxisome biogenesis |
| Desplats et al. (2014) | HIV+ METH+ (n = 13) vs. HIV+ no METH (n = 14) | Frontal cortex | DNA methylation array | METH increases global DNA methylation |
| Levine et al. (2016) | HIV+ with HAND (n = 43) vs. HIV+/CN (n = 15) | Dorso-lateral, medial frontal, occipital cortex | DNA methylation array | HIV affects epige-netic clock, HAND associated with accelerated aging |
| Plasma and peripheral blood | ||||
| Kadri et al. (2016) | HIV+ with NCI (n = 17) vs. HIV+/CN (n = 13) | Plasma | miRNA microarray, qRT-PCR | 4 miR pairs discern NCI from CN |
| Asahchop et al. (2016) | Discovery cohort: HIV+ HAND (n = 22) vs. HIV+/CN (n = 25) Validation cohort: HIV+ HAND (n = 12) vs. HIV+/CN (n = 12) | Plasma | miRNA microarray, qRT-PCR | miR-3665, miR-4516, miR-4707–5p/neural develop-ment, cell death, cytokine, genes |
| Shiau et al. (2021) | HIV+ (n = 69) vs. HIV−/Ctl (n = 38) | Peripheral blood | DNA methylation array | HIV accelerates epigenetic clock, impairs cognition |
| Total n in epigenetic studies | HIV+ with or without NCI or HIVE (n = 314) vs. HIV−/Ctl (n = 56) | |||