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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Fate of microglia during HIV‐1 infection: From activation to senescence?
Glia, v 65(3), pp 431-446
Mar 2017
PMCID: PMC5263094
PMID: 27888531
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Microglia support productive human immunodeficiency virus type 1 (HIV‐1) infection and disturbed microglial function could contribute to the development of HIV‐associated neurocognitive disorders (HAND). Better understanding of how HIV‐1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV‐1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging. We then critically discuss how HIV‐1 infection and exposure to viral proteins such as Tat and gp120 affect various aspects of microglial homeostasis including activation, cellular metabolism and cell cycle regulation, through pathways implicated in cellular stress responses including p38 mitogen‐activated protein kinase (MAPK) and nuclear factor κB (NF‐κB). We thus propose that the functions of human microglia evolve during both healthy and pathological aging. Aging‐associated dysfunction of microglia comprises phenotypes resembling cellular senescence, which could contribute to cognitive impairments observed in various neurodegenerative diseases. In addition, microglia seems to develop characteristics that could be related to cellular senescence post‐HIV‐1 infection and after exposure to HIV‐1 viral proteins. However, despite its potential role as a component of HAND and likely other neurocognitive disorders, microglia senescence has not been well characterized and should be the focus of future studies, which could have high translational relevance. GLIA 2017;65:431–446
Main Points
HIV‐1 infection and viral proteins increase microglia expression of activation markers and cell cycle inhibitors, and alter cellular metabolism.
Some of these phenotypes resemble cellular senescence.
Microglia senescence may thus contribute to HAND.
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Details
- Title
- Fate of microglia during HIV‐1 infection: From activation to senescence?
- Creators
- Natalie C. Chen - Drexel UniversityAndrea T. Partridge - Drexel UniversityChristian Sell - Drexel UniversityClaudio Torres - Drexel UniversityJulio Martín‐García - Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine
- Publication Details
- Glia, v 65(3), pp 431-446
- Publisher
- Wiley
- Number of pages
- 16
- Grant note
- The Aging Initiative at Drexel University College of Medicine Public Health Service Grants (NS065727) NIAID/NIH (AG046943) NIMH/NIH T32 NIA/NIH (NS078283) Interdisciplinary and Translational Research Training in NeuroAIDS NINDS/NIH (AI098549)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology; Neurobiology and Anatomy
- Web of Science ID
- WOS:000397106500001
- Scopus ID
- 2-s2.0-85002613579
- Other Identifier
- 991019168670204721
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- Web of Science research areas
- Neurosciences