title: 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.
authors: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors: Rebecca A
authors: RA
authors: Bozym
authors: Kunal
authors: K
authors: Patel
authors: Carl
authors: C
authors: White
authors: King-Ho
authors: KH
authors: Cheung
authors: Jeffrey M
authors: JM
authors: Bergelson
authors: Stefanie A
authors: SA
authors: Morosky
authors: Carolyn B
authors: CB
authors: Coyne
mesh_terms: D018938:Caco-2 Cells; D020013:Calcium Signaling; D002154:Calpain / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D029822:Enterovirus B, Human / Q000502:physiology*; D004769:Enterovirus Infections / Q000821:virology*; D057075:Enzyme Assays; D006367:HeLa Cells; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology / Q000821:virology*; D008856:Microscopy, Fluorescence; D009336:Necrosis / Q000378:metabolism / Q000821:virology*; D019108:Tight Junctions / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D057074:Virus Release
chemical_list: D036022:Capsid Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010738:Type C Phospholipases; C505407:CASP3 protein, human; D002154:Calpain; D053148:Caspase 3; C569870:CAPN2 protein, human