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

Rebecca A. Bozym, Kunal Patel, Carl White, King-Ho CHEUNG, JM Bergelson, Stefanie A. Morosky, Carolyn B. Coyne

Research output: Contribution to journalJournal articlepeer-review

39 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)3010-3021
Number of pages12
JournalMolecular Biology of the Cell
Volume22
Issue number17
DOIs
Publication statusPublished - Sept 2011

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