Telbivudine reduces parvovirus b19-induced apoptosis in circulating angiogenic cells

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.