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UPREGULATION OF SUPEROXIDE DISMUTASE 2 BY ASTROCYTES IN THE SIV/MACAQUE MODEL OF HIV-ASSOCIATED NEUROLOGIC DISEASE

By 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 Mankowski

Posted 06 May 2020
bioRxiv DOI: 10.1101/2020.05.05.078691 (published DOI: 10.1093/jnen/nlaa084)

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 co-localized 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 delay the onset or reduce severity of HAND seen in ART-treated HIV-infected patients. ### Competing Interest Statement The authors have declared no competing interest.

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