title: Proteomic landscape of bronchoalveolar lavage fluid in human immunodeficiency virus infection.
abstract: The lung is an important reservoir of human immunodeficiency virus (HIV). Individuals infected with HIV are more prone to pulmonary infections and chronic lung disorders. We hypothesized that comprehensively profiling the proteomic landscape of bronchoalveolar lavage fluid (BALF) in patients with HIV would provide insights into how this virus alters the lung milieu and contributes to pathogenesis of HIV-related lung diseases. BALF was obtained from five HIV-negative (HIV(-)) and six asymptomatic HIV-positive (HIV(+)) subjects not on antiretroviral therapy. Each sample underwent shotgun proteomic analysis based on HPLC-tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation to identify overlapping and distinct pathways enriched between the BALF proteome of HIV(+) and HIV(-) subjects. We identified a total of 318 unique proteins in BALF of HIV(-) and HIV(+) subjects. Of these, 87 were differentially up- or downregulated between the two groups. Many of these differentially expressed proteins are known to interact with key HIV proteins. Functional analysis of differentially regulated proteins implicated downregulation of immune responses in lungs of HIV(+) patients. Combining shotgun proteomic analysis with computational methods demonstrated that the BALF proteome is significantly altered during HIV infection. We found that immunity-related pathways are underrepresented in HIV(+) patients. These findings implicate mechanisms whereby HIV invokes local immunosuppression in the lung and increases the susceptibility of HIV(+) patients to develop a wide range of infectious and noninfectious pulmonary diseases.
authors.affiliation: Computational Medicine Core, Center for Lung Biology, 850 Mercer St., Box 358052, Seattle, WA 98109. sagharib@u.washington.edu.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Nguyen
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.forename: Kristina
authors.initials: K
authors.lastname: Crothers
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Chow
authors.forename: David R
authors.initials: DR
authors.lastname: Park
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Schnapp
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D054884:Host-Pathogen Interactions; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D020543:Proteome
keywords: immunity; mass spectrometry; pulmonary; shotgun proteomics