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

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. © 2006 by The National Academy of Sciences of the USA.

keywords 🔗 severe acute (1373) 🔗 highly pathogenic (100) 🔗 respiratory syndrome-associated (90) 🔗 infected cells (307) 🔗 membrane protein (93) 🔗 respiratory syndrome (2004) 🔗 results suggest (206) 🔗 acute respiratory (1734) 🔗 syndrome-associated coronavirus (88)

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