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Open AccessCommunication

Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells

Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
Department of Infectious Diseases, Robert-Koch-Institut, 13353 Berlin, Germany
Institut für Kardiale Diagnostik und Therapie (IKDT), 12203 Berlin, Germany
MEDIACC GmbH, 10713 Berlin, Germany
Berlin-Brandenburg Centre for Regenerative Therapies, 13353 Berlin, Germany
Author to whom correspondence should be addressed.
Viruses 2019, 11(3), 227;
Received: 26 January 2019 / Revised: 28 February 2019 / Accepted: 1 March 2019 / Published: 6 March 2019
(This article belongs to the Special Issue New Insights into Parvovirus Research)
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. View Full-Text
Keywords: telbivudine; B19V; circulating angiogenic cells; apoptosis; caspase-3; BIRC3 (cIAP-2) telbivudine; B19V; circulating angiogenic cells; apoptosis; caspase-3; BIRC3 (cIAP-2)
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Zobel, T.; Bock, C.-T.; Kühl, U.; Rohde, M.; Lassner, D.; Schultheiss, H.-P.; Schmidt-Lucke, C. Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells. Viruses 2019, 11, 227.

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