Abstract
Abuse of alcohol and tobacco could exacerbate HIV pathogenesis by transferring materials through exosomes (small nanovesicles). Exosomes present a stable and accessible source of information concerning the health and/or disease status of patients, which can provide diagnostic and prognostic biomarkers for myriad conditions. Therefore, we aimed to study the specific exosomal proteins that are altered in both HIV-infected subjects and alcohol/tobacco users. Exosomes were isolated from plasma of the following subjects: a) HIV-negative subjects (healthy), b) HIV-positive subjects (HIV), c) HIV-negative alcohol drinkers (drinkers), d) HIV-negative tobacco smokers (smokers), e) HIV-positive drinkers (HIV + drinkers), and f) HIV-positive smokers (HIV + smokers). Quantitative proteomic profiling was then performed from these exosomes. Sixteen proteins were significantly altered in the HIV group, ten in drinkers, four in HIV + drinkers, and fifteen in smokers compared to healthy subjects. Only one protein, fibulin-1 (FBLN1), was significantly altered in HIV + smokers. Interestingly, hemopexin was not significantly altered in drinkers or HIV patients but was significantly altered in HIV + drinkers. Further, our study is the first to show properdin expression in plasma exosomes, which was decreased in HIV + smokers and HIV + drinkers compared to HIV patients. The present findings suggest that hemopexin and properdin show potential as markers for physiological effects that may arise in HIV-infected individuals who abuse alcohol and tobacco.
This study presents a proteomic analysis of plasma-derived exosomes from HIV-infected alcohol drinkers and smokers. Among the proteins altered due to drug-abuse, hemopexin and properdin were of highest significance. These proteins can be potential biomarkers for co-morbid conditions associated with drug abuse in HIV-patients.
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Acknowledgements
We gratefully acknowledge the faculty and staff at the Molecular Research Center at UTHSC for their assistance in performing LC-MS/MS and statistical analysis of proteomics data. We also thank the National Institute on Alcohol Abuse and Alcoholism (AA022063) and National Institute on Drug Abuse (DA042374 and DA047178) for supporting our work.
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Supplementary Table S1
online: The list of proteins identified and quantified in all the studied groups (PDF 150 kb)
Supplementary Table S2
online: Significantly altered proteins in the study groups. a. Healthy Vs HIV-positive subjects. b. Healthy Vs Drinkers. c. Healthy vs HIV + drinkers. d. Healthy vs Smokers. e. Drinkers vs HIV + drinkers. f Smokers vs HIV + smokers. g. HIV vs HIV + drinkers. h. HIV vs HIV + smokers (PDF 113 kb)
Supplementary Table S3
online. Significantly enriched pathways according to DAVID analysis. a. Drinkers vs HIV+ Drinkers. b. Smokers vs HIV+ Smokers. c. HIV vs HIV+ Drinkers. d. HIV vs HIV+ Smokers (PDF 387 kb)
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Kodidela, S., Wang, Y., Patters, B.J. et al. Proteomic Profiling of Exosomes Derived from Plasma of HIV-Infected Alcohol Drinkers and Cigarette Smokers. J Neuroimmune Pharmacol 15, 501–519 (2020). https://doi.org/10.1007/s11481-019-09853-2
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DOI: https://doi.org/10.1007/s11481-019-09853-2