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,
Suzanne E Queen,
Posted 06 May 2020
bioRxiv DOI: 10.1101/2020.05.05.078691 (published DOI: 10.1093/jnen/nlaa084)
Posted 06 May 2020
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.
- Downloaded 337 times
- Download rankings, all-time:
- Site-wide: 110,341
- In neuroscience: 16,520
- Year to date:
- Site-wide: 73,759
- Since beginning of last month:
- Site-wide: 73,365
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!