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Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.

Abstract : Fourteen ORFs have been identified in the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) genome. ORF 3a of SARS-CoV codes for a recently identified transmembrane protein, but its function remains unknown. In this study we confirmed the 3a protein expression and investigated its localization at the surface of SARS-CoV-infected or 3a-cDNA-transfected cells. Our experiments showed that recombinant 3a protein can form a homotetramer complex through interprotein disulfide bridges in 3a-cDNA-transfected cells, providing a clue to ion channel function. The putative ion channel activity of this protein was assessed in 3a-complement RNA-injected Xenopus oocytes by two-electrode voltage clamp. The results suggest that 3a protein forms a potassium sensitive channel, which can be efficiently inhibited by barium. After FRhK-4 cells were transfected with an siRNA, which is known to suppress 3a expression, followed by infection with SARS-CoV, the released virus was significantly decreased, whereas the replication of the virus in the infected cells was not changed. Our observation suggests that SARS-CoV ORF 3a functions as an ion channel that may promote virus release. This finding will help to explain the highly pathogenic nature of SARS-CoV and to develop new strategies for treatment of SARS infection.
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Submitted on : Wednesday, September 7, 2011 - 3:41:17 AM
Last modification on : Tuesday, May 31, 2022 - 10:20:13 AM
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Wei Lu, Bo-Jian Zheng, Ke Xu, Wolfgang Schwarz, Lanying Du, et al.. Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.. Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2006, 103 (33), pp.12540-5. ⟨10.1073/pnas.0605402103⟩. ⟨pasteur-00619943⟩

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