title: HIV-1 differentially modulates autophagy in neurons and astrocytes.
abstract: Autophagy, a lysosomal degradative pathway that maintains cellular homeostasis, has emerged as an innate immune defense against pathogens. The role of autophagy in the deregulated HIV-infected central nervous system (CNS) is unclear. We have found that HIV-1-induced neuro-glial (neurons and astrocytes) damage involves modulation of the autophagy pathway. Neuro-glial stress induced by HIV-1 led to biochemical and morphological dysfunctions. X4 HIV-1 produced neuro-glial toxicity coupled with suppression of autophagy, while R5 HIV-1-induced toxicity was restricted to neurons. Rapamycin, a specific mTOR inhibitor (autophagy inducer) relieved the blockage of the autophagy pathway caused by HIV-1 and resulted in neuro-glial protection. Further understanding of the regulation of autophagy by cytokines and chemokines or other signaling events may lead to recognition of therapeutic targets for neurodegenerative diseases.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Mehla
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA. Electronic address: acniwar@gmail.com.
authors.forename: Ashok
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D001253:Astrocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D001343:Autophagy / Q000187:drug effects / Q000276:immunology*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D005333:Fetus; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
keywords: Autophagosomes; HIV astrocytes; HIV brain; HIV-1 neurotoxicity; HIV-infected macrophages; PSD-95