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Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells
Aims: Human parvovirus B19 (B19V) infection directly induces apoptosis and modulates CXCR4 expression of infected marrow-derived circulating angiogenic cells (CACs). This leads to dysfunctional endogenous vascular repair. Treatment for B19V-associated disease is restricted to symptomatic treatment....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466312/ https://www.ncbi.nlm.nih.gov/pubmed/30845701 http://dx.doi.org/10.3390/v11030227 |
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author | Zobel, Thomas Bock, C.-Thomas Kühl, Uwe Rohde, Maria Lassner, Dirk Schultheiss, Heinz-Peter Schmidt-Lucke, Caroline |
author_facet | Zobel, Thomas Bock, C.-Thomas Kühl, Uwe Rohde, Maria Lassner, Dirk Schultheiss, Heinz-Peter Schmidt-Lucke, Caroline |
author_sort | Zobel, Thomas |
collection | PubMed |
description | Aims: Human parvovirus B19 (B19V) infection directly induces apoptosis and modulates CXCR4 expression of infected marrow-derived circulating angiogenic cells (CACs). This leads to dysfunctional endogenous vascular repair. Treatment for B19V-associated disease is restricted to symptomatic treatment. Telbivudine, a thymidine analogue, established in antiviral treatment for chronic hepatitis B, modulates pathways that might influence induction of apoptosis. Therefore, we tested the hypothesis of whether telbivudine influences B19V-induced apoptosis of CAC. Methods and Results: Pretreatment of two CAC-lines, early outgrowth endothelial progenitor cells (eo-EPC) and endothelial colony-forming cells (ECFC) with telbivudine before in vitro infection with B19V significantly reduced active caspase-3 protein expression (−39% and −40%, both p < 0.005). Expression of Baculoviral Inhibitor of apoptosis Repeat-Containing protein 3 (BIRC3) was significantly downregulated by in vitro B19V infection in ECFC measured by qRT-PCR. BIRC3 downregulation was abrogated with telbivudine pretreatment (p < 0.001). This was confirmed by single gene PCR (p = 0.017) and Western blot analysis. In contrast, the missing effect of B19V on angiogenic gene expression postulates a post-transcriptional modulation of CXCR4. Conclusions: We for the first time show a treatment approach to reduce B19V-induced apoptosis. Telbivudine reverses B19V-induced dysregulation of BIRC3, thus, intervening in the apoptosis pathway and protecting susceptible cells from cell death. This approach could lead to an effective B19V treatment to reduce B19V-related disease. |
format | Online Article Text |
id | pubmed-6466312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64663122019-04-18 Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells Zobel, Thomas Bock, C.-Thomas Kühl, Uwe Rohde, Maria Lassner, Dirk Schultheiss, Heinz-Peter Schmidt-Lucke, Caroline Viruses Communication Aims: Human parvovirus B19 (B19V) infection directly induces apoptosis and modulates CXCR4 expression of infected marrow-derived circulating angiogenic cells (CACs). This leads to dysfunctional endogenous vascular repair. Treatment for B19V-associated disease is restricted to symptomatic treatment. Telbivudine, a thymidine analogue, established in antiviral treatment for chronic hepatitis B, modulates pathways that might influence induction of apoptosis. Therefore, we tested the hypothesis of whether telbivudine influences B19V-induced apoptosis of CAC. Methods and Results: Pretreatment of two CAC-lines, early outgrowth endothelial progenitor cells (eo-EPC) and endothelial colony-forming cells (ECFC) with telbivudine before in vitro infection with B19V significantly reduced active caspase-3 protein expression (−39% and −40%, both p < 0.005). Expression of Baculoviral Inhibitor of apoptosis Repeat-Containing protein 3 (BIRC3) was significantly downregulated by in vitro B19V infection in ECFC measured by qRT-PCR. BIRC3 downregulation was abrogated with telbivudine pretreatment (p < 0.001). This was confirmed by single gene PCR (p = 0.017) and Western blot analysis. In contrast, the missing effect of B19V on angiogenic gene expression postulates a post-transcriptional modulation of CXCR4. Conclusions: We for the first time show a treatment approach to reduce B19V-induced apoptosis. Telbivudine reverses B19V-induced dysregulation of BIRC3, thus, intervening in the apoptosis pathway and protecting susceptible cells from cell death. This approach could lead to an effective B19V treatment to reduce B19V-related disease. MDPI 2019-03-06 /pmc/articles/PMC6466312/ /pubmed/30845701 http://dx.doi.org/10.3390/v11030227 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Zobel, Thomas Bock, C.-Thomas Kühl, Uwe Rohde, Maria Lassner, Dirk Schultheiss, Heinz-Peter Schmidt-Lucke, Caroline Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells |
title | Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells |
title_full | Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells |
title_fullStr | Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells |
title_full_unstemmed | Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells |
title_short | Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells |
title_sort | telbivudine reduces parvovirus b19-induced apoptosis in circulating angiogenic cells |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466312/ https://www.ncbi.nlm.nih.gov/pubmed/30845701 http://dx.doi.org/10.3390/v11030227 |
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