Upregulation of Superoxide Dismutase 2 by Astrocytes in the SIV/Macaque Model of HIV-Associated Neurologic Disease

Michelle N. Sullivan, Samuel A. Brill, Lisa M. Mangus, Yea Ji Jeong, Clarisse V. Solis, Audrey C. Knight, Carlo Colantuoni, Gizem Keceli, Nazareno Paolocci, Suzanne E. Queen, Joseph L. Mankowski

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-associated neurocognitive disorders (HAND) remain prevalent despite implementation of antiretroviral therapy (ART). Development of HAND is linked to mitochondrial dysfunction and oxidative stress in the brain; therefore, upregulation of antioxidant defenses is critical to curtail neuronal damage. Superoxide dismutase 2 (SOD2) is a mitochondrial antioxidant enzyme essential for maintaining cellular viability. We hypothesized that SOD2 was upregulated during retroviral infection. Using a simian immunodeficiency virus (SIV)-infected macaque model of HIV, quantitative PCR showed elevated SOD2 mRNA in cortical gray ([GM], 7.6-fold for SIV vs uninfected) and white matter ([WM], 77-fold for SIV vs uninfected) during SIV infection. Further, SOD2 immunostaining was enhanced in GM and WM from SIV-infected animals. Double immunofluorescence labeling illustrated that SOD2 primarily colocalized with astrocyte marker glial fibrillary acidic protein (GFAP) in SIV-infected animals. Interestingly, in ART-treated SIV-infected animals, brain SOD2 RNA levels were similar to uninfected animals. Additionally, using principal component analysis in a transcriptomic approach, SOD2 and GFAP expression separated SIV-infected from uninfected brain tissue. Projection of these data into a HIV dataset revealed similar expression changes, thereby validating the clinical relevance. Together, our findings suggest that novel SOD2-enhancing therapies may reduce neuroinflammation in ART-treated HIV-infected patients.

Original languageEnglish (US)
Pages (from-to)986-997
Number of pages12
JournalJournal of neuropathology and experimental neurology
Volume79
Issue number9
DOIs
StatePublished - Sep 1 2020

Keywords

  • Astrocytes
  • HIV
  • SOD2

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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