Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells
| Autor: | Caroline Schmidt-Lucke, Uwe Kühl, Dirk Lassner, Thomas Zobel, Heinz-Peter Schultheiss, C-Thomas Bock, Maria Rohde |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death Receptors CXCR4 caspase-3 B19V lcsh:QR1-502 Caspase 3 030204 cardiovascular system & hematology Inhibitor of apoptosis Virus Replication CXCR4 Antiviral Agents lcsh:Microbiology Cell Line 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Virology Telbivudine medicine Parvovirus B19 Human Humans ddc:610 Progenitor cell Angiogenic Proteins business.industry Communication BIRC3 (cIAP-2) apoptosis Endothelial Cells Baculoviral IAP Repeat-Containing 3 Protein 030104 developmental biology Infectious Diseases circulating angiogenic cells Apoptosis DNA Viral Cancer research telbivudine business 610 Medizin und Gesundheit medicine.drug Signal Transduction |
| Zdroj: | Viruses, Vol 11, Iss 3, p 227 (2019) Viruses |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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