{"doi":"10.1101/2020.05.05.078691","title":"UPREGULATION OF SUPEROXIDE DISMUTASE 2 BY ASTROCYTES IN THE SIV/MACAQUE MODEL OF HIV-ASSOCIATED NEUROLOGIC DISEASE","abstract":"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 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126624,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":425061,"name":"Samuel A. Brill","orcid":null,"position":1,"is_corresponding":false},{"id":475216,"name":"Lisa M. Mangus","orcid":"0000-0002-3896-517X","position":2,"is_corresponding":false},{"id":294308,"name":"Yea Ji Jeong","orcid":"0000-0002-4665-5446","position":3,"is_corresponding":false},{"id":425062,"name":"Clarisse V. Solis","orcid":null,"position":4,"is_corresponding":false},{"id":423586,"name":"Audrey C. Knight","orcid":"0000-0002-8009-8081","position":5,"is_corresponding":false},{"id":59071,"name":"Carlo Colantuoni","orcid":"0000-0001-6818-6380","position":6,"is_corresponding":false},{"id":424710,"name":"Gizem Keceli","orcid":"0000-0002-9562-7994","position":7,"is_corresponding":false},{"id":383581,"name":"Nazareno Paolocci","orcid":"0000-0001-7011-997X","position":8,"is_corresponding":false},{"id":423587,"name":"Suzanne E. Queen","orcid":"0009-0001-7220-5254","position":9,"is_corresponding":false},{"id":409612,"name":"Joseph L. Mankowski","orcid":"0000-0002-6283-4727","position":10,"is_corresponding":false},{"id":513776,"name":"Michelle N. Sullivan","orcid":"0009-0005-1971-0672","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}