Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release
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| Název: | Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release |
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| Autoři: | Deubel, V, Xu, K, Schwarz, W, Du, L, Wong, CKL, Duan, S, Sun, B, Lu, W, Zheng, B, Chen, J |
| Zdroj: | Proceedings of the National Academy of Sciences |
| Informace o vydavateli: | Proceedings of the National Academy of Sciences, 2006. |
| Rok vydání: | 2006 |
| Témata: | 0301 basic medicine, Rna, Small Interfering - Genetics - Metabolism, Patch-Clamp Techniques, Oocytes - Cytology - Physiology, Virus Replication, Ion Channels, Cell Line, Viroporin Proteins, Open Reading Frames, Viral Proteins, Xenopus laevis, 03 medical and health sciences, Viral Envelope Proteins, Xenopus Laevis, Ion Channels - Genetics - Metabolism, Animals, Humans, RNA, Small Interfering, Recombinant Proteins - Genetics - Metabolism, Potassium - Metabolism, Multidisciplinary, Viral Proteins - Genetics - Metabolism, Recombinant Proteins, 3. Good health, Severe acute respiratory syndrome-related coronavirus, Oocytes, Potassium, Sars Virus - Genetics - Metabolism |
| Popis: | 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-injectedXenopusoocytes 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. |
| Druh dokumentu: | Article Conference object |
| Jazyk: | English |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0605402103 |
| Přístupová URL adresa: | https://www.pnas.org/content/pnas/103/33/12540.full.pdf https://pubmed.ncbi.nlm.nih.gov/16894145 https://www.pnas.org/content/103/33/12540.full.pdf https://pubmed.ncbi.nlm.nih.gov/16894145/ https://pure.mpg.de/pubman/faces/ViewItemOverviewPage.jsp?itemId=item_2080539 https://www.pnas.org/content/pnas/103/33/12540.full.pdf https://www.ncbi.nlm.nih.gov/pubmed/16894145 https://ui.adsabs.harvard.edu/abs/2006PNAS..10312540L/abstract http://hdl.handle.net/10722/157455 |
| Přístupové číslo: | edsair.doi.dedup.....248d8705e5825b62e4e2d660ece192b1 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | 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-injectedXenopusoocytes 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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| ISSN: | 10916490 00278424 |
| DOI: | 10.1073/pnas.0605402103 |