Calcium Signals and Calpain-dependent Necrosis Are Essential for Release of Coxsackievirus B from Polarized Intestinal Epithelial Cells

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2011 Jul 9

PMID 21737691

Citations 27

Authors

Rebecca A Bozym

Kunal Patel

Carl White

King-Ho Cheung

Jeffrey M Bergelson

Stefanie A Morosky

Carolyn B Coyne

Affiliations

Soon will be listed here.

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.

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