@article {47686,
	title = {The open reading frame 3a protein of severe acute respiratory syndrome-associated coronavirus promotes membrane rearrangement and cell death.},
	journal = {Journal of virology},
	volume = {84},
	year = {2010},
	month = {2010 Jan},
	pages = {1097-109},
	abstract = {<p>The genome of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains eight open reading frames (ORFs) that encode novel proteins. These accessory proteins are dispensable for in vitro and in vivo replication and thus may be important for other aspects of virus-host interactions. We investigated the functions of the largest of the accessory proteins, the ORF 3a protein, using a 3a-deficient strain of SARS-CoV. Cell death of Vero cells after infection with SARS-CoV was reduced upon deletion of ORF 3a. Electron microscopy of infected cells revealed a role for ORF 3a in SARS-CoV induced vesicle formation, a prominent feature of cells from SARS patients. In addition, we report that ORF 3a is both necessary and sufficient for SARS-CoV-induced Golgi fragmentation and that the 3a protein accumulates and localizes to vesicles containing markers for late endosomes. Finally, overexpression of ADP-ribosylation factor 1 (Arf1), a small GTPase essential for the maintenance of the Golgi apparatus, restored Golgi morphology during infection. These results establish an important role for ORF 3a in SARS-CoV-induced cell death, Golgi fragmentation, and the accumulation of intracellular vesicles.</p>
},
	keywords = {ADP-Ribosylation Factor 1, Animals, Cell Death, Cell Membrane, Cercopithecus aethiops, Cytoplasmic Vesicles, Gene Deletion, Golgi Apparatus, Host-Pathogen Interactions, Humans, SARS Virus, Transfection, Vero Cells, Viral Structural Proteins},
	issn = {1098-5514},
	doi = {10.1128/JVI.01662-09},
	author = {Freundt, Eric C and Yu, Li and Goldsmith, Cynthia S and Welsh, Sarah and Cheng, Aaron and Yount, Boyd and Liu, Wei and Frieman, Matthew B and Buchholz, Ursula J and Screaton, Gavin R and Lippincott-Schwartz, Jennifer and Zaki, Sherif R and Xu, Xiao-Ning and Baric, Ralph S and Subbarao, Kanta and Lenardo, Michael J}
}
