title: Fate of microglia during HIV-1 infection: From activation to senescence?
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.
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania.|MD/PhD Program, Drexel University College of Medicine, Philadelphia, Pennsylvania.|Molecular and Cell Biology and Genetics Graduate Program, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania.|Microbiology and Immunology Graduate Program, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Partridge
authors.affiliation: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Christian
authors.initials: C
authors.lastname: Sell
authors.affiliation: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Claudio
authors.initials: C
authors.lastname: Torres
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Julio
authors.identifier: 0000-0001-5450-5029
authors.initials: J
authors.lastname: Martín-García
mesh_terms: D000375:Aging; D000818:Animals; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D017628:Microglia / Q000378:metabolism* / Q000821:virology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: HAND; cellular senescence; chronic infection; microglia dysfunction