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Neuroinflammatory Profiling in SIV-Infected Chinese-Origin Rhesus Macaques on Antiretroviral Therapy

Solis-Leal, Antonio
; 
Siddiqui, Summer
; 
Wu, Fei
; 
Mohan, Mahesh
; ; 
Doyle-Meyers, Lara A.
; 
Dufour, Jason P.
; 
Ling, Binhua
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Genre
Journal article
Date
2022-01-13
Advisor
Committee member
Group
Center for Metabolic Disease Research (Temple University)
Department
Pathology and Laboratory Medicine
Subject
Human immunodeficiency virus
 Simian immunodeficiency virus
 Central nervous system
 Reservoir
 Antiretroviral therapy
 Non-human primates
 Rhesus macaques
 Immune activation
 Neuroinflammation
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http://hdl.handle.net/20.500.12613/9288
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HuEtAl-JournalArticle-2022-01.pdf
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DOI
http://dx.doi.org/10.3390/v14010139
Abstract
The central nervous system (CNS) HIV reservoir is an obstacle to achieving an HIV cure. The basal ganglia harbor a higher frequency of SIV than other brain regions in the SIV-infected rhesus macaques of Chinese-origin (chRMs) even on suppressive combination antiretroviral therapy (ART). Since residual HIV/SIV reservoir is associated with inflammation, we characterized the neuroinflammation by gene expression and systemic levels of inflammatory molecules in healthy controls and SIV-infected chRMs with or without ART. CCL2, IL-6, and IFN-γ were significantly reduced in the cerebrospinal fluid (CSF) of animals receiving ART. Moreover, there was a correlation between levels of CCL2 in plasma and CSF, suggesting the potential use of plasma CCL2 as a neuroinflammation biomarker. With higher SIV frequency, the basal ganglia of untreated SIV-infected chRMs showed an upregulation of secreted phosphoprotein 1 (SPP1), which could be an indicator of ongoing neuroinflammation. While ART greatly reduced neuroinflammation in general, proinflammatory genes, such as IL-9, were still significantly upregulated. These results expand our understanding of neuroinflammation and signaling in SIV-infected chRMs on ART, an excellent model to study HIV/SIV persistence in the CNS.
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Citation
Solis-Leal, A.; Siddiqui, S.; Wu, F.; Mohan, M.; Hu, W.; Doyle-Meyers, L.A.; Dufour, J.P.; Ling, B. Neuroinflammatory Profiling in SIV-Infected Chinese-Origin Rhesus Macaques on Antiretroviral Therapy. Viruses 2022, 14, 139. https://doi.org/10.3390/v14010139
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Viruses, Vol. 14, Iss. 1
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