Calcium Flux between the Endoplasmic Reticulum and Mitochondrion Contributes to Poliovirus-Induced Apoptosis

Abstract

We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca2+) concentration in neuroblastoma IMR5 cells, at least partly through Ca2+ release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) channels. This leads to Ca2+ accumulation in mitochondria through the mitochondrial Ca2+ uniporter and the voltage-dependent anion channel (VDAC). This increase in mitochondrial Ca2+ concentration in PV-infected cells leads to mitochondrial dysfunction and apoptosis.

The CREB3-Herp signalling module limits the cytosolic calcium concentration increase and apoptosis induced by poliovirus

“…The decrease in Herp levels followed the same dynamics as the previously described increase in cytosolic Ca 2+ concentration during PV infection associated with cell progression to apoptosis (Brisac et al, 2010). We found that Herp restricted the PV-induced increase in cytosolic Ca 2+ concentration.…”

“…These values were also normalized against those for mock-infected cells (n-fold increase/mock). chromatin condensation and fragmentation by flow cytometry, as previously described (Brisac et al, 2010;Estaquier et al, 1994). As expected, the time course of PV-induced apoptosis (Fig.…”

“…Herp protein levels increased as early as 1 h post-infection (p.i.) and for up to 4 h p.i., corresponding to the early phase of PV replication in IMR5 cells (Brisac et al, 2010). Then, Herp protein levels decreased.…”

“…As a positive control, cells were treated with TG. At the indicated times p.i., cytosolic Ca 2+ levels were determined by flow cytometry, as previously described (Brisac et al, 2010). As expected, PV infection resulted in an increase in cytosolic Ca 2+ concentration, which was significant from 6 h p.i.…”

“…We have previously showed that this event was driven by a balance between pro-and anti-apoptotic signals: the JNK and PI3K pathways, respectively (Autret et al, 2007(Autret et al, , 2008. The apoptotic programme initiated by PV infection also involves calcium (Ca 2+ ) flux from the endoplasmic reticulum (ER) lumen to the cytosol, via the ER-resident Ca 2+ channels IP 3 R (inositol 1,4,5-triphosphate receptor) and RyR (ryanodine receptor) (Brisac et al, 2010). These channels have been implicated in apoptotic Ca 2+ signalling in several models of viral infection (for a review, see Chami et al, 2006).…”