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.
Highlights
Introduction iationsIn the era of antiretroviral therapy (ART), HIV-induced neuronal injury and loss is a great concern for HIV patients as it causes cognitive, motor, and behavioral dysfunction
We observed that ART significantly reduced levels of some proinflammatory cytokines in peripheral blood and cerebrospinal fluid (CSF) of SIV-infected chRMs (Figures 1 and 2), while others were not affected by the treatment
The present study has shown that ART may alleviate neuroinflammation in SIVinfected chRMs by modulating the levels and expression of some inflammation-related genes and neuroimmune activation pathways
Summary
Animals were housed at the Tulane National Primate Research Center (TNPRC) and maintained following the standards of the American Association for Accreditation of Laboratory Animal Care and the “Guide for the Care and Use of Laboratory Animals”. Institutional Animal Care and Use Committee (IACUC). A total of 19 Rhesus macaques (Macaca mulatta) of Chinese origin were used in this study. They were divided into 3 groups, the SIV-naïve healthy group (control, n = 5), SIV-infected without ART (untreated, n = 7), and SIV-infected with ART (ART, n = 7). Animals were sera-negative for SIV, simian D retrovirus, and simian T-cell leukemia virus before SIV inoculation. Except for the healthy control group, the animals in the other two groups were inoculated intravenously with
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