Dataset Information

Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells.

ABSTRACT: Coxsackievirus B (CVB), a member of the enterovirus family, targets the polarized epithelial cells lining the intestinal tract early in infection. Although the polarized epithelium functions as a protective barrier, this barrier is likely exploited by CVB to promote viral entry and subsequent egress. Here we show that, in contrast to nonpolarized cells, CVB-infected polarized intestinal Caco-2 cells undergo nonapoptotic necrotic cell death triggered by inositol 1,4,5-trisphosphate receptor-dependent calcium release. We further show that CVB-induced cellular necrosis depends on the Ca(2+)-activated protease calpain-2 and that this protease is involved in CVB-induced disruption of the junctional complex and rearrangements of the actin cytoskeleton. Our study illustrates the cell signaling pathways hijacked by CVB, and perhaps other viral pathogens, to promote their replication and spread in polarized cell types.

SUBMITTER: Bozym RA

PROVIDER: S-EPMC3164450 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells.

Bozym Rebecca A RA Patel Kunal K White Carl C Cheung King-Ho KH Bergelson Jeffrey M JM Morosky Stefanie A SA Coyne Carolyn B CB

Molecular biology of the cell 20110707 17

Coxsackievirus B (CVB), a member of the enterovirus family, targets the polarized epithelial cells lining the intestinal tract early in infection. Although the polarized epithelium functions as a protective barrier, this barrier is likely exploited by CVB to promote viral entry and subsequent egress. Here we show that, in contrast to nonpolarized cells, CVB-infected polarized intestinal Caco-2 cells undergo nonapoptotic necrotic cell death triggered by inositol 1,4,5-trisphosphate receptor-depen ...[more]

PMID: 21737691

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Project description:In cardiac myocytes, excitation-contraction coupling depends upon sarcoplasmic reticular Ca2+ release triggered by Ca2+ influx through L-type Ca2+ channels. Although Na+-Ca2+ exchange (NCX) is essential for Ca2+ extrusion, its participation in the trigger process of excitation-contraction coupling is controversial. To investigate the role of NCX in triggering, we examined Ca2+ sparks in ventricular cardiomyocytes isolated from wild-type (WT) and cardiac-specific NCX knockout (KO) mice. Myocytes from young NCX KO mice are known to exhibit normal resting cytosolic Ca2+ and normal Ca2+ transients despite reduced L-type Ca2+ current. We loaded myocytes with fluo-3 to image Ca2+ sparks using confocal microscopy in line-scan mode. The frequency of spontaneous Ca2+ sparks was reduced in KO myocytes compared with WT. However, spark amplitude and width were increased in KO mice. Permeabilizing the myocytes with saponin eliminated differences between spontaneous sparks in WT and KO mice. These results suggest that sarcolemmal processes are responsible for the reduced spark frequency and increased spark width and amplitude in KO mice. When myocytes were loaded with 1 mM fluo-3 and 3 mM EGTA via the patch pipette to buffer diadic cleft Ca2+, the number of sparks triggered by action potentials was reduced by 60% in KO cells compared to WT cells, despite similar SR Ca2+ content in both cell types. When EGTA was omitted from the pipette solution, the number of sparks triggered in KO and WT myocytes was similar. Although the number of sparks was restored in KO cells, Ca2+ release was asynchronous. These results suggest that high subsarcolemmal Ca2+ is required to ensure synchronous triggering with short spark latency in the absence of NCX. In WT mice, high subsarcolemmal Ca2+ is not required for synchronous triggering, because NCX is capable of priming the diadic cleft with sufficient Ca2+ for normal triggering, even when subsarcolemmal Ca(2+) is lowered by EGTA. Thus, reducing subsarcolemmal Ca2+ with EGTA in NCX KO mice reveals the dependence of Ca2+ release on NCX.

Dataset Information

Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells.

Publications

Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells.

Similar Datasets

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