id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-287892-bnqmwst8	Hyser, Joseph M.	Rotavirus Disrupts Calcium Homeostasis by NSP4 Viroporin Activity	2010-11-30		.txt	text/plain	7093	397	49	The rotavirus nonstructural protein 4 (NSP4), an endoplasmic reticulum (ER) transmembrane glycoprotein, increases intracellular levels of cytoplasmic Ca(2+) ([Ca(2+)]cyto) through a phospholipase C-independent pathway, which is required for virus replication and morphogenesis. We identified an NSP4 domain (amino acids [aa] 47 to 90) that inserts into membranes and has structural characteristics of viroporins, a class of small hydrophobic viral proteins that disrupt membrane integrity and ion homeostasis to facilitate virus entry, assembly, or release. In epithelial cells, expression of wild-type NSP4 increased the levels of free cytoplasmic Ca(2+) by 3.7-fold, but NSP4 viroporin mutants maintained low levels of [Ca(2+)]cyto, were retained in the ER, and failed to form cytoplasmic vesicular structures, called puncta, which surround viral replication and assembly sites in rotavirus-infected cells. We previously showed that NSP4 forms a novel vesicular compartment concomitantly with increased [Ca 2ϩ ]cyto (45) and that these structures associate with the autophagy protein LC3 and surround viroplasms, cytoplasmic inclusions in rotavirus-infected cells that support virus replication.	./cache/cord-287892-bnqmwst8.txt	./txt/cord-287892-bnqmwst8.txt