Abstract
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 Statement
The authors have declared no competing interest.
List of abbreviations
- cART
- combination antiretroviral therapy
- HIV
- human immunodeficiency virus type 1
- HAND
- human immunodeficiency virus type 1-associated neurocognitive disorders
- SIV
- Simian immunodeficiency virus
- CNS
- central nervous system
- neuroAIDS
- neurological complications of HIV acquired immunodeficiency syndrome
- SIVE
- SIV-associated encephalitis
- SAIDS
- simian AIDS
- PARPs
- poly(ADP-ribose) polymerases
- SGS
- single genome sequencing
- RNA
- ribonucleic acid
- mRNA
- messenger RNA
- qPCR
- quantitative polymerase chain reaction
- GAPDH
- Glyceraldehyde 3-phosphate dehydrogenase
- DV
- detectable SIV in the brain
- NDV
- low/undetectable SIV in the brain
- DEGs
- differentially expressed genes
- NPAS
- Neuronal PAS Domain Protein
- EPSTI
- epithelial stromal interaction
- SLFN
- Schlafen Family Member
- MAMU-A
- major histocompatibility complex, class I, A (Rhesus monkey)
- IFN
- interferon
- ISGs
- type I interferon-stimulated genes
- DDX
- DExD/H-Box Helicase
- RIG1
- retinoic acid-inducible gene I
- PSMB
- Proteasome 20S Subunit Beta
- NCF
- Neutrophil Cytosolic Factor
- STAT
- Signal Transducer And Activator Of Transcription
- CSF1
- Colony Stimulating Factor 1
- CSF1R
- Colony Stimulating Factor 1 receptor
- MNDA
- myeloid cell nuclear differentiation antigen
- MIF
- Macrophage migration inhibitory factor
- IFI
- Interferon Induced Protein
- IRF
- Interferon Regulatory Factor
- MX1
- MX Dynamin Like GTPase 1
- OAS1
- 2’-5’-Oligoadenylate Synthetase 1
- TLR
- toll-like receptor
- NADPH
- Reduced nicotinamide adenine dinucleotide phosphate
- C1Q
- complement component 1q
- C3
- complement component 3
- TNFSF10
- TNF Superfamily Member 10