PT  - JOURNAL ARTICLE
AU  - Carla Mavian
AU  - Andrea S. Ramirez-Mata
AU  - James Jarad Dollar
AU  - David J. Nolan
AU  - Shannan N. Rich
AU  - Kevin White
AU  - Brittany Rife Magalis
AU  - Melanie Cash
AU  - Simone Marini
AU  - Mattia C. F. Prosperi
AU  - David Moraga Amador
AU  - Alberto Riva
AU  - Kenneth C. Williams
AU  - Marco Salemi
TI  - Brain tissue transcriptomic analysis of SIV-infected macaques identifies Poly (ADP-ribose) polymerases (PARPs) as potential biomarkers for neuropathogenesis
AID  - 10.1101/2020.05.21.109140
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.21.109140
4099  - http://biorxiv.org/content/early/2020/05/24/2020.05.21.109140.short
4100  - http://biorxiv.org/content/early/2020/05/24/2020.05.21.109140.full
AB  - Background Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals’ quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified.Results We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n=11), with or without CD8+ lymphocyte depletion, based on detectable (n=6) or non-detectable (n=5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction.Conclusions Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology.Competing Interest StatementThe authors have declared no competing interest.cARTcombination antiretroviral therapyHIVhuman immunodeficiency virus type 1HANDhuman immunodeficiency virus type 1-associated neurocognitive disordersSIVSimian immunodeficiency virusCNScentral nervous systemneuroAIDSneurological complications of HIV acquired immunodeficiency syndromeSIVESIV-associated encephalitisSAIDSsimian AIDSPARPspoly(ADP-ribose) polymerasesSGSsingle genome sequencingRNAribonucleic acidmRNAmessenger RNAqPCRquantitative polymerase chain reactionGAPDHGlyceraldehyde 3-phosphate dehydrogenaseDVdetectable SIV in the brainNDVlow/undetectable SIV in the brainDEGsdifferentially expressed genesNPASNeuronal PAS Domain ProteinEPSTIepithelial stromal interactionSLFNSchlafen Family MemberMAMU-Amajor histocompatibility complex, class I, A (Rhesus monkey)IFNinterferonISGstype I interferon-stimulated genesDDXDExD/H-Box HelicaseRIG1retinoic acid-inducible gene IPSMBProteasome 20S Subunit BetaNCFNeutrophil Cytosolic FactorSTATSignal Transducer And Activator Of TranscriptionCSF1Colony Stimulating Factor 1CSF1RColony Stimulating Factor 1 receptorMNDAmyeloid cell nuclear differentiation antigenMIFMacrophage migration inhibitory factorIFIInterferon Induced ProteinIRFInterferon Regulatory FactorMX1MX Dynamin Like GTPase 1OAS12’-5’-Oligoadenylate Synthetase 1TLRtoll-like receptorNADPHReduced nicotinamide adenine dinucleotide phosphateC1Qcomplement component 1qC3complement component 3TNFSF10TNF Superfamily Member 10