Next Article in Journal
Molecular Phylogeny of Mobatviruses (Hantaviridae) in Myanmar and Vietnam
Next Article in Special Issue
A New Prevalent Densovirus Discovered in Acari. Insight from Metagenomics in Viral Communities Associated with Two-Spotted Mite (Tetranychus urticae) Populations
Previous Article in Journal
Genetic Susceptibility to Human Norovirus Infection: An Update
Previous Article in Special Issue
Methylation Status of the Adeno-Associated Virus Type 2 (AAV2)
Open AccessCommunication

Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells

1
Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
2
Department of Infectious Diseases, Robert-Koch-Institut, 13353 Berlin, Germany
3
Institut für Kardiale Diagnostik und Therapie (IKDT), 12203 Berlin, Germany
4
MEDIACC GmbH, 10713 Berlin, Germany
5
Berlin-Brandenburg Centre for Regenerative Therapies, 13353 Berlin, Germany
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(3), 227; https://doi.org/10.3390/v11030227
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)
Show Figures

Figure 1

MDPI and ACS Style

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop