Characterization of Nef expression in different brain regions of SIV-infected macaques.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
05
2020
accepted:
19
10
2020
entrez:
2
11
2020
pubmed:
3
11
2020
medline:
22
12
2020
Statut:
epublish
Résumé
HIV-associated CNS dysfunction is a significant problem among people with HIV (PWH), who now live longer due to viral suppression from combined anti-retroviral therapy (ART). Over the course of infection, HIV generates toxic viral proteins and induces inflammatory cytokines that have toxic effects on neurons in the CNS. Among these viral proteins, HIV Nef has been found in neurons of postmortem brain specimens from PWH. However, the source of Nef and its impact on neuronal cell homeostasis are still elusive. Here, in using a simian immunodeficiency virus (SIV) infected rhesus macaque model of neuroHIV, we find SIV Nef reactivity in the frontal cortex, hippocampus and cerebellum of SIV-infected animals using immunohistochemistry (IHC). Interestingly, SIV-infected macaques treated with ART also showed frequent Nef positive cells in the cerebellum and hippocampus. Using dual quantitative RNAscope and IHC, we observed cells that were positive for Nef, but were not for SIV RNA, suggesting that Nef protein is present in cells that are not actively infected with SIV. Using cell specific markers, we observed Nef protein in microglia/macrophages and astrocytes. Importantly, we also identified a number of NeuN-positive neurons, which are not permissive to SIV infection, but contained Nef protein. Further characterization of Nef-positive neurons showed caspase 3 activation, indicating late stage apoptosis in the CNS neurons. Our results suggest that regardless of ART status, Nef is expressed in the brain of SIV infected macaques and may contribute to neurological complications seen in PWH.
Identifiants
pubmed: 33137166
doi: 10.1371/journal.pone.0241667
pii: PONE-D-20-12456
pmc: PMC7605674
doi:
Substances chimiques
Gene Products, nef
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0241667Subventions
Organisme : NIMH NIH HHS
ID : P30 MH092177
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH079785
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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