title: HIV Infects Bronchial Epithelium and Suppresses Components of the Mucociliary Clearance Apparatus.
abstract: Recurrent lung infections and pneumonia are emerging as significant comorbidities in the HIV-infected population in the era of combination antiretroviral therapy (cART). HIV infection has been reported to suppress nasal mucociliary clearance (MCC). Since the primary components driving nasal MCC and bronchial MCC are identical, it is possible that bronchial MCC is affected as well. Effective MCC requires optimal ciliary beating which depends on the maintenance of the airway surface liquid (ASL), a function of cystic fibrosis transmembrane conductance regulator (CFTR) activity and the integrity of the signaling mechanism that regulates ciliary beating and fluid secretion. Impairment of either component of the MCC apparatus can compromise its efficacy and promote microbial colonization. We demonstrate that primary bronchial epithelium expresses HIV receptor CD4 and co-receptors CCR5 and CXCR4 and can be infected by both R5 and X4 tropic strains of HIV. We show that HIV Tat suppresses CFTR biogenesis and function in primary bronchial epithelial cells by a pathway involving TGF-β signaling. HIV infection also interferes with bronchial epithelial cell differentiation and suppresses ciliogenesis. These findings suggest that HIV infection suppresses tracheobronchial mucociliary clearance and this may predispose HIV-infected patients to recurrent lung infections, pneumonia and chronic bronchitis.
authors.affiliation: Department of Immunology, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University. Miami, Florida, United States of America.
authors.forename: S
authors.initials: S
authors.lastname: Chinnapaiyan
authors.affiliation: Department of Immunology, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University. Miami, Florida, United States of America.
authors.forename: T
authors.initials: T
authors.lastname: Parira
authors.affiliation: Department of Immunology, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University. Miami, Florida, United States of America.
authors.forename: R
authors.initials: R
authors.lastname: Dutta
authors.affiliation: Department of Immunology, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University. Miami, Florida, United States of America.
authors.forename: M
authors.initials: M
authors.lastname: Agudelo
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: A
authors.initials: A
authors.lastname: Morris
authors.affiliation: Department of Immunology, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University. Miami, Florida, United States of America.
authors.forename: M
authors.initials: M
authors.lastname: Nair
authors.affiliation: Department of Immunology, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University. Miami, Florida, United States of America.
authors.forename: H J
authors.initials: HJ
authors.lastname: Unwalla
mesh_terms: D002923:Cilia / Q000473:pathology / Q000821:virology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D009079:Mucociliary Clearance / Q000276:immunology*; D011533:Proviruses; D012367:RNA, Viral; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D048348:Reverse Transcription; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D012367:RNA, Viral; D015728:Receptors, HIV; D016212:Transforming Growth Factor beta; D054322:tat Gene Products, Human Immunodeficiency Virus; D019005:Cystic Fibrosis Transmembrane Conductance Regulator