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Autophagy. 2013 May;9(5):797-8. doi: 10.4161/auto.23959. Epub 2013 Feb 26.

Viroporin-mediated calcium-activated autophagy.

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  • 1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.

Abstract

Autophagy is a cellular response activated by many pathogens, but the mechanism of activation is largely unknown. Recently we showed for the first time that rotavirus initiates the autophagy pathway through a calcium-mediated mechanism. Expression of the rotavirus-encoded NSP4, a pore-forming protein (viroporin), elicits the release of endoplasmic reticulum (ER) lumenal calcium into the cytoplasm of the infected cell. The increased cytoplasmic calcium activates a calcium signaling pathway involving calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and 5' adenosine monophosphate-activated protein kinase (AMPK) to trigger autophagy. Rotavirus further manipulates autophagy membrane trafficking to transport viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly. Transport of viral proteins to viroplasms is required for assembly of infectious virus. Thus, NSP4, a multifunctional viral protein known to regulate infectious particle assembly, also modulates membrane trafficking by orchestrating the activation of autophagy to benefit viral replication.

KEYWORDS:

autophagy; calcium; kinase; stress; virus

PMID:
23442576
[PubMed - indexed for MEDLINE]
PMCID:
PMC3669193
Free PMC Article
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