title: HIV infection model of chronic obstructive pulmonary disease in mice.
abstract: Cigarette smoke usage is prevalent in human immunodeficiency virus (HIV)-positive patients, and, despite highly active antiretroviral therapy, these individuals develop an accelerated form of chronic obstructive pulmonary disease (COPD). Studies investigating the mechanisms of COPD development in HIV have been limited by the lack of suitable mouse models. Here we describe a model of HIV-induced COPD in wild-type mice using EcoHIV, a chimeric HIV capable of establishing chronic infection in immunocompetent mice. A/J mice were infected with EcoHIV and subjected to whole body cigarette smoke exposure. EcoHIV was detected in alveolar macrophages of mice. Compared with uninfected mice, concomitant EcoHIV infection significantly reduced forced expiratory flow 50%/forced vital capacity and enhanced distal airspace enlargement following cigarette smoke exposure. Lung IL-6, granulocyte-macrophage colony-stimulating factor, neutrophil elastase, cathepsin G, and matrix metalloproteinase-9 expression was significantly enhanced in smoke-exposed EcoHIV-infected mice. These changes coincided with enhanced IκBα, ERK1/2, p38, and STAT3 phosphorylation and lung cell apoptosis. Thus, the EcoHIV smoke exposure mouse model reproduces several of the pathophysiological features of HIV-related COPD in humans, indicating that this murine model can be used to determine key parameters of HIV-related COPD and to test future therapies for this disorder.
authors.affiliation: Division of Pulmonary & Critical Care Medicine, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York.|Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York; and.
authors.forename: Patrick
authors.initials: P
authors.lastname: Geraghty
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Eran
authors.initials: E
authors.lastname: Hadas
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Boe-Hyun
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Division of Pulmonary & Critical Care Medicine, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York.|Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York; and.
authors.forename: Abdoulaye J
authors.initials: AJ
authors.lastname: Dabo
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: David J
authors.initials: DJ
authors.lastname: Volsky
authors.affiliation: Division of Pulmonary & Critical Care Medicine, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York; Robert.Foronjy@downstate.edu.|Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Foronjy
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000821:virology; D016676:Macrophages, Alveolar / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011014:Pneumonia / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D012907:Smoking / Q000009:adverse effects
chemical_list: D010447:Peptide Hydrolases
keywords: animal model; cigarette smoke; human immunodeficiency virus