Journal article
Induction of a Senescence-Like Phenotype in Cultured Human Fetal Microglia During HIV-1 Infection
The journals of gerontology. Series A, Biological sciences and medical sciences, v 73(9), pp 1187-1196
01 Sep 2018
PMID: 29415134
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
HIV-1 causes premature aging in chronically infected patients. Despite effective anti-retroviral therapy, around 50% of patients suffer HIV-associated neurocognitive disorders (HAND), which likely potentiate aging-associated neurocognitive decline. Microglia support productive HIV-1 infection in the brain. Elevated markers of cellular senescence, including p53 and p21, have been detected in brain tissues from patients with HAND, but the potential for microglia senescence during HIV-1 infection has not been investigated. We hypothesized that HIV-1 can induce senescence in microglia. Primary human fetal microglia were exposed to single-round infectious HIV-1 pseudotypes or controls, and examined for markers of senescence. Post-infection, microglia had significantly elevated: senescence-associated beta-galactosidase activity, p21 levels, and production of cytokines such as IL-6 and IL-8, potentially indicative of a senescence-associated secretory phenotype. We also found increased detection of p53-binding protein foci in microglia nuclei post-infection. Additionally, we examined mitochondrial reactive oxygen species (ROS) and respiration, and found significantly increased mitochondrial ROS levels and decreased ATP-linked respiration during HIV-1 infection. Supernatant transfer from infected cultures to naive microglia resulted in elevated p21 and caveolin-1 levels, and IL-8 production. Finally, nucleoside treatment reduced senescence markers induction in microglia. Overall, HIV-1 induces a senescence-like phenotype in human microglia, which could play a role in HAND.
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Details
- Title
- Induction of a Senescence-Like Phenotype in Cultured Human Fetal Microglia During HIV-1 Infection
- Creators
- Natalie C. Chen - Department of Microbiology and Immunology, Philadelphia, PennsylvaniaAndrea T. Partridge - Department of Microbiology and Immunology, Philadelphia, PennsylvaniaFerit Tuzer - Department of Pathology and Laboratory Medicine, Philadelphia, Pennsylvania.Justin Cohen - Molecular and Cell Biology and Genetics Graduate Program, Philadelphia, PennsylvaniaTimothy Nacarelli - Molecular and Cell Biology and Genetics Graduate Program, Philadelphia, PennsylvaniaSonia Navas-Martin - Drexel UniversityChristian Sell - Drexel UniversityClaudio Torres - Drexel UniversityJulio Martin-Garcia - Drexel University
- Publication Details
- The journals of gerontology. Series A, Biological sciences and medical sciences, v 73(9), pp 1187-1196
- Publisher
- Oxford Univ Press
- Number of pages
- 10
- Grant note
- NS065727; AI098549; AG051296; NS078283; NS078283-S1; AG046943 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA internal Drexel funds T32 MH079785 / National Institutes of Health, Interdisciplinary and Translational Research Training in NeuroAIDS R01NS104365 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Drexel University Aging Initiative Fellowship T32MH079785 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) F31AG054191 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology; Neurobiology and Anatomy
- Web of Science ID
- WOS:000441747200006
- Scopus ID
- 2-s2.0-85055320514
- Other Identifier
- 991019167422604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Geriatrics & Gerontology
- Gerontology