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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....

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Autores principales: Zobel, Thomas, Bock, C.-Thomas, Kühl, Uwe, Rohde, Maria, Lassner, Dirk, Schultheiss, Heinz-Peter, Schmidt-Lucke, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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