The Golgi protein ACBD3, an interactor for poliovirus protein 3A, modulates poliovirus replication.

We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication.

Calcium flux between the endoplasmic reticulum and mitochondrion contributes to poliovirus-induced apoptosis.

We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca(2+)) concentration in neuroblastoma IMR5 cells, at least partly through Ca(2+) release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP(3)R) and ryanodine receptor (RyR) channels. This leads to Ca(2+) accumulation in mitochondria through the mitochondrial Ca(2+) uniporter and the voltage-dependent anion channel (VDAC). This increase in mitochondrial Ca(2+) concentration in PV-infected cells leads to mitochondrial dysfunction and apoptosis.

Bcl-2 family proteins and mitochondrial fission/fusion dynamics.

Mitochondria are dynamic organelles and can undergo regulated fission/fragmentation to produce smaller organelles or, alternatively, can undergo fusion to produce tubular or net-like mitochondrial structures. Although some of the molecules that control mitochondrial fission and fusion are known, new molecules and pathways that control this process continue to be discovered, suggesting that this process is more complex than previously appreciated. In addition to their crucial role in the regulation of apoptosis, recent studies have implicated members of the Bcl-2 family in maintenance of the mitochondrial network.

Emerging role for members of the Bcl-2 family in mitochondrial morphogenesis.

Bcl-2 family proteins regulate apoptosis by controlling the release of mitochondrial cytochrome c via the Bax/Bak channel. However, recent studies have also implicated several members of this family in the regulation of mitochondrial fission/fusion dynamics. It has been debated whether the role of Bcl-2 proteins in mitochondrial morphogenesis is functionally distinct from their role in apoptosis, with some arguing that Bax/Bak-induced mitochondrial fission promotes apoptosis-associated cytochrome c release, while others suggest that these functions are separable.

Apoptotic signaling cascades operating in poliovirus-infected cells.

The flaccid paralyses characteristic of poliomyelitis are a direct consequence of the infection of motor neurons with poliovirus (PV). In PV-infected mice, motor neurons die by apoptosis. However, the mechanisms by which PV induces cell death in neurons remain unclear.

Development of a Taqman RT-PCR assay for the detection and quantification of negatively stranded RNA of human enteroviruses: evidence for false-priming and improvement by tagged RT-PCR.

Human enteroviruses are among the most common viruses infecting humans. These viruses are known to be able to infect a wide range of tissues and are believed to establish persistent infections. Enteroviruses are positive-sense single-stranded RNA viruses whose replication involves the synthesis of negative strand intermediates.

Early phosphatidylinositol 3-kinase/Akt pathway activation limits poliovirus-induced JNK-mediated cell death.

Poliovirus (PV)-induced apoptosis seems to play a major role in tissue injury in the central nervous system (CNS). We have previously shown that this process involves PV-induced Bax-dependent mitochondrial dysfunction mediated by early JNK activation in IMR5 neuroblastoma cells. We showed here that PV simultaneously activates the phosphatidylinositol 3-kinase (PI3K)/Akt survival signaling pathway in these cells, limiting the extent of JNK activation and thereby cell death.

Prevention and treatment of enteric viral infections: possible benefits of probiotic bacteria.

The structure and function of the intestinal epithelium is briefly described, with the principal mechanisms involved in diarrhea. Human enteric viruses and probiotics are presented. We then review how probiotic bacteria could interfere with virus-induced pathology, we present our own view and describe specific interactions that would be valuable targets for future studies.

Poliovirus induces Bax-dependent cell death mediated by c-Jun NH2-terminal kinase.

Poliovirus (PV) is the causal agent of paralytic poliomyelitis, a disease that involves the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through an apoptotic process. However, mechanisms by which PV induces cell death in neuronal cells remain unclear.

Bax is activated during rotavirus-induced apoptosis through the mitochondrial pathway.

Rotaviruses are the leading cause of infantile viral gastroenteritis worldwide. Mature enterocytes of the small intestine infected by rotavirus undergo apoptosis, and their replacement by less differentiated dividing cells probably leads to defective absorptive function of the intestinal epithelium, which, in turn, contributes to osmotic diarrhea and rotavirus pathogenesis. Here we show that infection of MA104 cells by the simian rhesus rotavirus strain RRV induced caspase-3 activation, DNA fragmentation, and cleavage of poly(ADP-ribose) polymerase; all three phenomena are features of apoptosis.