Plasma proteome analysis reveals overlapping, yet distinct mechanisms of immune activation in chronic HCV and HIV infections
| Autor: | Fred E. Hazlett, Nicholas T. Funderburg, Julia M. Sugalski, Michael M. Lederman, Scott F. Sieg, Donald D. Anthony, Jill S. Barnholtz-Sloan, Mark R. Chance, Yanwen Chen, Daniela Schlatzer, Perica Davitkov, Benigno Rodriguez |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Proteome CD14 T cell Aspartate transaminase HIV Infections Biology CD38 Article Liver disease Plasma medicine Humans Pharmacology (medical) Coinfection virus diseases Hepatitis C Chronic Middle Aged medicine.disease Virology Cyclic Nucleotide Phosphodiesterases Type 2 Infectious Diseases medicine.anatomical_structure Immunology biology.protein Female Autotaxin Lysophospholipids Biomarkers |
| Zdroj: | Journal of acquired immune deficiency syndromes (1999). 63(5) |
| ISSN: | 1944-7884 |
| Popis: | Background HIV infection contributes to accelerated rates of progression of liver fibrosis during hepatitis C virus (HCV) infection, and HCV liver disease contributes to mortality during HIV infection. Although mechanisms underlying these interactions are not well known, soluble and cellular markers of immune activation associate with disease progression during both infections. Methods We identified proteins varying in expression across the plasma proteomes of subjects with untreated HIV infection, untreated HCV infection with low aspartate transaminase/platelet ratio index, untreated HCV infection with high aspartate transaminase/platelet ratio index, HIV-HCV coinfection, and controls. We examined correlations between dysregulated proteins and markers of immune activation to uncover biomarkers specific to disease states. Results We observed the anticipated higher frequencies of HLA-DRCD38CD4 and CD8 T cells, higher serum soluble CD14 levels, and higher serum interleukin-6 levels for HCV- and HIV-infected groups compared with controls. Plasma proteome analysis identified 2297 peptides mapping to 227 proteins, and quantitative analysis of peptide intensity identified significant changes in 85 proteins across the 5 groups. Abundance for 7 of these proteins was validated by enzyme-linked immunosorbent assay. Forty-three of these proteins correlated with markers of immune activation, including at least 2 proteins that may directly drive T-cell activation. As a functional validation, we tested the enzymatic pathway product (lysophosphatidic acid, LPA) of one such protein, ecotonucleotide pyrophosphatase/phosphodiesterase-2, for ability to activate T cells in vitro. LPA activated T cells to express CD38 and HLA-DR. Conclusions These data indicate that elevated levels of ecotonucleotide pyrophosphatase/phosphodiesterase-2 and LPA during advanced HCV disease may play a role in exacerbating immune activation during HCV-HIV coinfection. |
| Databáze: | OpenAIRE |
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