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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.

SUBMITTER: Nguyen EV

PROVIDER: S-EPMC3920210 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Proteomic landscape of bronchoalveolar lavage fluid in human immunodeficiency virus infection.

Nguyen Elizabeth V EV Gharib Sina A SA Crothers Kristina K Chow Yu-Hua YH Park David R DR Goodlett David R DR Schnapp Lynn M LM

American journal of physiology. Lung cellular and molecular physiology 20131108 1

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 ...[more]

PMID: 24213920

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Project description:BackgroundIt is now possible to comprehensively characterize the microbiota of the lungs using culture-independent, sequencing-based assays. Several sample types have been used to investigate the lung microbiota, each presenting specific challenges for preparation and analysis of microbial communities. Bronchoalveolar lavage fluid (BALF) enables the identification of microbiota specific to the lower lung but commonly has low bacterial density, increasing the risk of false-positive signal from contaminating DNA. The objectives of this study were to investigate the extent of contamination across a range of sample densities representative of BALF and identify features of contaminants that facilitate their removal from sequence data and aid in the interpretation of BALF sample 16S sequencing data.ResultsUsing three mock communities across a range of densities ranging from 8E+?02 to 8E+?09 16S copies/ml, we assessed taxonomic accuracy and precision by 16S rRNA gene sequencing and the proportion of reads arising from contaminants. Sequencing accuracy, precision, and the relative abundance of mock community members decreased with sample input density, with a significant drop-off below 8E+?05 16S copies/ml. Contaminant OTUs were commonly inversely correlated with sample input density or not reproduced between technical replicates. Removal of taxa with these features or physical concentration of samples prior to sequencing improved both sequencing accuracy and precision for samples between 8E+?04 and 8E+?06 16S copies/ml. For the lowest densities, below 8E+?03 16S copies/ml BALF, accuracy and precision could not be significantly improved using these approaches. Using clinical BALF samples across a large density range, we observed that OTUs with features of contaminants identified in mock communities were also evident in low-density BALF samples.ConclusionRelative abundance data and community composition generated by 16S sequencing of BALF samples across the range of density commonly observed in this sample type should be interpreted in the context of input sample density and may be improved by simple pre- and post-sequencing steps for densities above 8E+?04 16S copies/ml.

Dataset Information

Proteomic landscape of bronchoalveolar lavage fluid in human immunodeficiency virus infection.

Publications

Proteomic landscape of bronchoalveolar lavage fluid in human immunodeficiency virus infection.

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