Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C InfectionSummary
Background & Aims: Hepatitis C virus (HCV) cell entry is mediated by several cell surface receptors, including scavenger receptor class B type I (SR-BI). Oxidized low density lipoprotein (oxLDL) inhibits the interaction between HCV and SR-BI in a noncompetitive manner. We tested whether serum ox...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-05-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X15000582 |
| _version_ | 1828374958310424576 |
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| author | Philipp Solbach Sandra Westhaus Maximilian Deest Eva Herrmann Thomas Berg Michael P. Manns Sandra Ciesek Christoph Sarrazin Thomas von Hahn |
| author_facet | Philipp Solbach Sandra Westhaus Maximilian Deest Eva Herrmann Thomas Berg Michael P. Manns Sandra Ciesek Christoph Sarrazin Thomas von Hahn |
| author_sort | Philipp Solbach |
| collection | DOAJ |
| description | Background & Aims: Hepatitis C virus (HCV) cell entry is mediated by several cell surface receptors, including scavenger receptor class B type I (SR-BI). Oxidized low density lipoprotein (oxLDL) inhibits the interaction between HCV and SR-BI in a noncompetitive manner. We tested whether serum oxLDL levels correlate with sustained virologic response (SVR) rates after interferon-based treatment of chronic hepatitis C. Methods: Baseline oxLDL was determined in 379 participants with chronic HCV genotype 1 infection from the INDIV-2 study using a commercial enzyme-linked immunosorbent assay. The mechanistic in vitro studies used full-length and subgenomic HCV genomes replicating in hepatoma cells. Results: In the multivariate analysis, oxLDL was found to be an independent predictor of SVR. Oxidized LDL did not correlate with markers of inflammation (alanine transaminase, ferritin), nor was serum oxLDL affected by exogenous interferon administration. Also, oxLDL did not alter the sensitivity of HCV replication to interferon. However, oxLDL was found to be a potent inhibitor of cell-to-cell spread of HCV between adjacent cells in vitro. It could thus reduce the rate at which new cells are infected by HCV through either the cell-free or cell-to-cell route. Finally, serum oxLDL was significantly associated with the estimated infected cell loss rate under treatment. Conclusions: Oxidized LDL is a novel predictor of SVR after interferon-based therapy and may explain the previously observed association of LDL with SVR. Rather than being a marker of activated antiviral defenses it may improve chances of SVR by limiting spread of infection to naive cells through the cell-to-cell route. Keywords: Cell-to-Cell Spread, oxLDL, SVR, SR-BI |
| first_indexed | 2024-04-14T07:40:53Z |
| format | Article |
| id | doaj.art-f3b30547f7254928a70b892ccba5d061 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-04-14T07:40:53Z |
| publishDate | 2015-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-f3b30547f7254928a70b892ccba5d0612022-12-22T02:05:31ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2015-05-0113285294.e1Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C InfectionSummaryPhilipp Solbach0Sandra Westhaus1Maximilian Deest2Eva Herrmann3Thomas Berg4Michael P. Manns5Sandra Ciesek6Christoph Sarrazin7Thomas von Hahn8Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, Germany; Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, Germany; Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, GermanyInstitute of Biostatistics and Mathematical Modeling, Johann-Wolfgang-Goethe-Universität, Frankfurt am Main, GermanyHepatology Section, Department of Gastroenterology and Rheumatology, Universitätsklinikum Leipzig, Leipzig, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, GermanyGerman Center for Infection Research (DZIF), Hannover, Germany; Medical Clinic I, Zentrum der Inneren Medizin, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt am Main, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, Germany; Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, Germany; Correspondence Address correspondence to: Thomas von Hahn, MD, Medizinische Hochschule Hannover, Institut für Molekularbiologie, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. fax: +49 511 532-4896.Background & Aims: Hepatitis C virus (HCV) cell entry is mediated by several cell surface receptors, including scavenger receptor class B type I (SR-BI). Oxidized low density lipoprotein (oxLDL) inhibits the interaction between HCV and SR-BI in a noncompetitive manner. We tested whether serum oxLDL levels correlate with sustained virologic response (SVR) rates after interferon-based treatment of chronic hepatitis C. Methods: Baseline oxLDL was determined in 379 participants with chronic HCV genotype 1 infection from the INDIV-2 study using a commercial enzyme-linked immunosorbent assay. The mechanistic in vitro studies used full-length and subgenomic HCV genomes replicating in hepatoma cells. Results: In the multivariate analysis, oxLDL was found to be an independent predictor of SVR. Oxidized LDL did not correlate with markers of inflammation (alanine transaminase, ferritin), nor was serum oxLDL affected by exogenous interferon administration. Also, oxLDL did not alter the sensitivity of HCV replication to interferon. However, oxLDL was found to be a potent inhibitor of cell-to-cell spread of HCV between adjacent cells in vitro. It could thus reduce the rate at which new cells are infected by HCV through either the cell-free or cell-to-cell route. Finally, serum oxLDL was significantly associated with the estimated infected cell loss rate under treatment. Conclusions: Oxidized LDL is a novel predictor of SVR after interferon-based therapy and may explain the previously observed association of LDL with SVR. Rather than being a marker of activated antiviral defenses it may improve chances of SVR by limiting spread of infection to naive cells through the cell-to-cell route. Keywords: Cell-to-Cell Spread, oxLDL, SVR, SR-BIhttp://www.sciencedirect.com/science/article/pii/S2352345X15000582 |
| spellingShingle | Philipp Solbach Sandra Westhaus Maximilian Deest Eva Herrmann Thomas Berg Michael P. Manns Sandra Ciesek Christoph Sarrazin Thomas von Hahn Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C InfectionSummary Cellular and Molecular Gastroenterology and Hepatology |
| title | Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C InfectionSummary |
| title_full | Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C InfectionSummary |
| title_fullStr | Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C InfectionSummary |
| title_full_unstemmed | Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C InfectionSummary |
| title_short | Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C InfectionSummary |
| title_sort | oxidized low density lipoprotein is a novel predictor of interferon responsiveness in chronic hepatitis c infectionsummary |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X15000582 |
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