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Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release
Author(s) -
van Kuppeveld Frank J.M.,
Hoenderop Joost G.J.,
Smeets Rolf L.L.,
Willems Peter H.G.M.,
Dijkman Henri B.P.M.,
Galama Jochem M.D.,
Melchers Willem J.G.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.12.3519
Subject(s) - endoplasmic reticulum , library science , biology , genetics , computer science
Digital‐imaging microscopy was performed to study the effect of Coxsackie B3 virus infection on the cytosolic free Ca 2+ concentration and the Ca 2+ content of the endoplasmic reticulum (ER). During the course of infection a gradual increase in the cytosolic free Ca 2+ concentration was observed, due to the influx of extracellular Ca 2+ . The Ca 2+ content of the ER decreased in time with kinetics inversely proportional to those of viral protein synthesis. Individual expression of protein 2B was sufficient to induce the influx of extracellular Ca 2+ and to release Ca 2+ from ER stores. Analysis of mutant 2B proteins showed that both a cationic amphipathic α‐helix and a second hydrophobic domain in 2B were required for these activities. Consistent with a presumed ability of protein 2B to increase membrane permeability, viruses carrying a mutant 2B protein exhibited a defect in virus release. We propose that 2B gradually enhances membrane permeability, thereby disrupting the intracellular Ca 2+ homeostasis and ultimately causing the membrane lesions that allow release of virus progeny.