Table 2.
Molecular pathways deregulated in in vitro and in vivo studies
| Cells | Pathways involving differentially regulated genes in HIV infection/disease progression | Subgroups | References | |
|---|---|---|---|---|
| In vivo | CD4+ | -Interferon-stimulated genes (ISGs), SYNCRIP, EPSTI1, MRPS18B | RP vs EC/ VNP | [57•] |
| -Apoptosis, lymphocyte activation, and IL1 activation | ||||
| -Chemokines/cytokines and their receptors | V-ART vs C | [34•] | ||
| -Genes impacting cell cycle | ||||
| -Regulation of immune activation | EC vs C | [34•] | ||
| -Components of mitogen-activated protein kinase (MAPK)/focal adhesion kinase (FAK) pathway, transcripts involved in cell cycle regulation | EC-ART vs EC-NC | [34•] | ||
| -Genes required to produce sustained virus production, assembly, and release | V/AV vs C | [36] | ||
| -Transcriptional modulation and RNA processing | ||||
| -Protein modification and trafficking | ||||
| CD8+ | -Multiple members of proteasome | RP vs EC | [9, 57•, 67, 68] | |
| -Interferon-stimulated immuno-proteasome and ISGs, weak CTL response | ||||
| -Cell cycle and cell division, metabolic genes indicating diminished cell proliferation | ||||
| Monocytes | -Apoptosis/DNA damage and cell cycle | V (therapy naive) vs C | [12•] | |
| -Lipid metabolism | ||||
| -Proteasome activity (cysteine-type endopeptidase activity, proteolysis ubiquitin cycle, ubiquitin-protein ligase activity) | ||||
| -Protein trafficking (protein import into nucleus) | ||||
| -Transcriptional regulation (DNA binding, negative regulation of transcription, transcription regulator activity) | ||||
| -Genes modulated by HIV, persistent (PTGER2, KLF10, FCGR3A) | V (therapy naïve) vs ART-treated | [12•] | ||
| -Genes modulated by HIV, reversible (CD83, HLA-DRA, BCL6, CDKN1A, MARCKS, STAT1a, STAT1b, NAMPT, PDGFC, CCL2) | ||||
| -Immune activation, anti-apoptotic (cis), pro-apoptotic (trans) and cell cycle | V (therapy naïve) vs infected | [12•] | ||
| -Protein trafficking and transcriptional regulation and metabolic dysregulation | ||||
| -Anti-apoptotic gene signatures | V vs C | [11] | ||
| -TNF-α signaling and CD40L/CD40 signaling, MAPK signaling, p53 modulation | ||||
| PBMCs | -MAPK signaling pathway (JUND), T-cell trafficking and differentiation (ID1, KLF2) | V vs AV | [32] | |
| -Cytokine signaling and interferon signaling (EIF2AK2, IFITM1) | ||||
| -Apoptosis related (PRF1) | ||||
| -Immune response, immature T-cell differentiation, changing immune homeostasis | P (grouped) | [53] | ||
| -Apoptosis, HIV replication | ||||
| Ex vivo | CD3+/CD4 + &CD8+ | -Cell cycle (specifically to mitosis phase, nucleic acid metabolic processes, and regulation to cell cycle progression), cell apoptosis and cell cycle dysregulation | P vs C/ LTNP | [10•,33, 69] |
| -Endogenous stimulus response (DNA damage stimulus and DNA repair) | ||||
| -Interferon responses as a signature of progression | ||||
| -Metabolism and energy production (TCA, OXOPHOS) | ||||
| In vitro | T cells | -Cell surface adhesion glycoprotein | Resistant vs Wt | [19] |
| -Interferon signaling, transcription factors | ||||
| -Cell division and transcription family of DEAD box helicases, transcriptional regulation | HIV-infected vs C | [17, 18, 70] | ||
| -Enzymes involved in cholesterol biosynthesis, cell activation and transcription factors, proapoptotic genes, expression of p53-induced product Bax, activation of caspase 2, 3, and 9 | ||||
| -Genes involved in translation and splicing | ||||
| -T-cell signaling, subcellular trafficking | ||||
| Mono/ MDMs | -Anti-apoptotic gene signatures, p53 modulation (p21) | HIV-infected/ gp120 exposed vs C | [11, 20, 21] | |
| -TNF-α signaling (CCL2, IER3) | ||||
| -CD40L/CD40 signaling (MTs, CD153), | ||||
| -ERK/MAPK network associated, including genes induced by CCR5, signaling (NRAS, LYN) |
AV, aviremic; C, healthy/negative controls; EC, elite controllers; LTNP, long-term non-progressors; P, progressors; RP, rapid progressors; V, viremic; VNP, viremic non-progressors