title: The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons.
abstract: Neurotoxicity of human immunodeficiency virus-1 (HIV) includes synaptic simplification and neuronal apoptosis. However, the mechanisms of HIV-associated neurotoxicity remain unclear, thus precluding an effective treatment of the neurological complications. The present study was undertaken to characterize novel mechanisms of HIV neurotoxicity that may explain how HIV subjects develop neuronal degeneration. Several neurodegenerative disorders are characterized by mitochondrial dysfunction; therefore, we hypothesized that HIV promotes mitochondrial damage. We first analyzed brains from HIV encephalitis (HIVE) by electron microscopy. Several sections of HIVE subjects contained enlarged and damaged mitochondria compared to brains from HIV subjects with no neurological complications. Similar pathologies were observed in mice overexpressing the HIV protein gp120, suggesting that this viral protein may be responsible for mitochondrial pathology found in HIVE. To gain more information about the cellular mechanisms of gp120 neurotoxicity, we exposed rat cortical neurons to gp120 and we determined cellular oxygen consumption rate, mitochondrial distribution, and trafficking. Our data show that gp120 evokes impairment in mitochondrial function and distribution. These data suggest that one of the mechanisms of HIV neurotoxicity includes altered mitochondrial dynamics in neurons.
authors.affiliation: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Avdoshina
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Jerel Adam
authors.initials: JA
authors.lastname: Fields
authors.affiliation: Department of Microbiology and Molecular Genetics, Public Health Research Institute Center and at the International Center for Public Health New Jersey Medical School - Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Castellano
authors.affiliation: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Dedoni
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Palchik
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Trejo
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Microbiology and Molecular Genetics, Public Health Research Institute Center and at the International Center for Public Health New Jersey Medical School - Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Eugenin
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA.|Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Italo
authors.initials: I
authors.lastname: Mocchetti
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D015331:Cohort Studies; D055032:Electron Microscope Tomography; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000633:toxicity*; D015658:HIV Infections / Q000150:complications / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020258:Neurotoxicity Syndromes / Q000235:genetics / Q000473:pathology*; D051381:Rats; D023701:Smegmamorpha; D013997:Time Factors
chemical_list: D015699:HIV Envelope Protein gp120; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C514793:gp120 protein, Human immunodeficiency virus 1; D049452:Green Fluorescent Proteins
keywords: Fis-1; Gp120ADA; HIVE; Mitochondrial respiration; Oxygen consumption; Tom 20