2. Academic Validation
  3. Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells

Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells

  • Viruses. 2019 Mar 6;11(3):227. doi: 10.3390/v11030227.
Thomas Zobel 1,  C-Thomas Bock 2,  Uwe Kühl 3,  Maria Rohde 4,  Dirk Lassner 5,  Heinz-Peter Schultheiss 6 7,  Caroline Schmidt-Lucke 8 9 10
Affiliations

Affiliations

  • 1 Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. thomas.zobel@mediacc.de.
  • 2 Department of Infectious Diseases, Robert-Koch-Institut, 13353 Berlin, Germany. thomas.bock@mediacc.de.
  • 3 Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. uwe.kuhl@mediacc.de.
  • 4 Institut für Kardiale Diagnostik und Therapie (IKDT), 12203 Berlin, Germany. maria.rohde@mediacc.de.
  • 5 Institut für Kardiale Diagnostik und Therapie (IKDT), 12203 Berlin, Germany. irk.lassner@mediacc.de.
  • 6 Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. schultheiss@mediacc.de.
  • 7 Institut für Kardiale Diagnostik und Therapie (IKDT), 12203 Berlin, Germany. schultheiss@mediacc.de.
  • 8 Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. caroline.schmidt-lucke@mediacc.org.
  • 9 MEDIACC GmbH, 10713 Berlin, Germany. caroline.schmidt-lucke@mediacc.org.
  • 10 Berlin-Brandenburg Centre for Regenerative Therapies, 13353 Berlin, Germany. caroline.schmidt-lucke@mediacc.org.
PMID: 30845701 DOI: 10.3390/v11030227
Abstract

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.

Keywords

B19V; BIRC3 (cIAP-2); apoptosis; caspase-3; circulating angiogenic cells; telbivudine.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z