The Open Reading Frame 3a Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Promotes Membrane Rearrangement and Cell Death

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  • Freundt, Eric C.
    • Other Affiliation: National Institutes of Health
  • Yu, Li
    • Other Affiliation: National Institutes of Health
  • Goldsmith, Cynthia S.
    • Other Affiliation: Center for Disease Control and Prevention
  • Welsh, Sarah
    • Other Affiliation: National Institutes of Health
  • Cheng, Aaron
    • Other Affiliation: National Institutes of Health
  • Youn, Boyd
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Liu, Wei
    • Other Affiliation: National Institutes of Health
  • Frieman, Matthew B.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Buchholz, Ursula J.
    • Other Affiliation: National Institutes of Health
  • Screaton, Savin R.
    • Other Affiliation: Imperial College
  • Lippincott-Schwartz, Jennifer
    • Other Affiliation: National Institutes of Health
  • Zaki, Sherif
    • Other Affiliation: National Institutes of Health
  • Xu, Xiao-Ning
    • Other Affiliation: University of Oxford
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Subbarao, Kanta
    • Other Affiliation: National Institutes of Health
  • Lenardo, Michael J.
    • Other Affiliation: National Institutes of Health
Abstract
  • 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.
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  • Article
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  • In Copyright
Journal title
  • Journal of Virology
Journal volume
  • 84
Journal issue
  • 2
Page start
  • 1097
Page end
  • 1109
Language
  • English
ISSN
  • 0022-538X

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