Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2006 Aug 15;10333:12540-5. doi: 10.1073/pnas.0605402103.
Show Gene links
Show Anatomy links
Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.
Lu W, Zheng BJ, Xu K, Schwarz W, Du L, Wong CK, Chen J, Duan S, Deubel V, Sun B.
???displayArticle.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.
Ciampor,
Influenza virus M2 protein and haemagglutinin conformation changes during intracellular transport.
1995, Pubmed
Ciampor,
Influenza virus M2 protein and haemagglutinin conformation changes during intracellular transport.
1995,
Pubmed Corse,
Infectious bronchitis virus E protein is targeted to the Golgi complex and directs release of virus-like particles.
2000,
Pubmed Drosten,
Identification of a novel coronavirus in patients with severe acute respiratory syndrome.
2003,
Pubmed Ewart,
The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels.
1996,
Pubmed Göttlinger,
Vpu protein of human immunodeficiency virus type 1 enhances the release of capsids produced by gag gene constructs of widely divergent retroviruses.
1993,
Pubmed Göttlinger,
Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release.
1991,
Pubmed He,
Inhibition of SARS-associated coronavirus infection and replication by RNA interference.
2003,
Pubmed Hsu,
Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel.
2004,
Pubmed Huang,
Severe acute respiratory syndrome coronavirus 3a protein is released in membranous structures from 3a protein-expressing cells and infected cells.
2006,
Pubmed Ito,
Severe acute respiratory syndrome coronavirus 3a protein is a viral structural protein.
2005,
Pubmed Kelly,
Demonstrating the intrinsic ion channel activity of virally encoded proteins.
2003,
Pubmed Kerschensteiner,
Fluorescence measurements reveal stoichiometry of K+ channels formed by modulatory and delayed rectifier alpha-subunits.
2005,
Pubmed Kotevic,
Constitutive interaction of the P2Y2 receptor with the hematopoietic cell-specific G protein G(alpha16) and evidence for receptor oligomers.
2005,
Pubmed Ksiazek,
A novel coronavirus associated with severe acute respiratory syndrome.
2003,
Pubmed Law,
The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells.
2005,
Pubmed Maeda,
Release of coronavirus E protein in membrane vesicles from virus-infected cells and E protein-expressing cells.
1999,
Pubmed Marra,
The Genome sequence of the SARS-associated coronavirus.
2003,
Pubmed Montal,
Structure-function correlates of Vpu, a membrane protein of HIV-1.
2003,
Pubmed Piller,
Vpr protein of human immunodeficiency virus type 1 forms cation-selective channels in planar lipid bilayers.
1996,
Pubmed Pinto,
Influenza virus M2 protein has ion channel activity.
1992,
Pubmed
,
Xenbase Plugge,
A potassium channel protein encoded by chlorella virus PBCV-1.
2000,
Pubmed
,
Xenbase Reynolds,
Rational siRNA design for RNA interference.
2004,
Pubmed Schubert,
Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells.
1996,
Pubmed
,
Xenbase Shen,
The severe acute respiratory syndrome coronavirus 3a is a novel structural protein.
2005,
Pubmed Shi,
Atomic structure of a Na+- and K+-conducting channel.
2006,
Pubmed Sugrue,
Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel.
1991,
Pubmed Tan,
Overexpression of 7a, a protein specifically encoded by the severe acute respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent pathway.
2004,
Pubmed Tan,
A novel severe acute respiratory syndrome coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis.
2004,
Pubmed Yu,
Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus.
2004,
Pubmed Yuan,
Subcellular localization and membrane association of SARS-CoV 3a protein.
2005,
Pubmed Zeng,
Characterization of the 3a protein of SARS-associated coronavirus in infected vero E6 cells and SARS patients.
2004,
Pubmed Zheng,
Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus.
2004,
Pubmed Zheng,
Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.
2005,
Pubmed
