Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.
Identifieur interne : 003D03 ( Main/Exploration ); précédent : 003D02; suivant : 003D04Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.
Auteurs : Wei Lu [République populaire de Chine] ; Bo-Jian Zheng ; Ke Xu ; Wolfgang Schwarz ; Lanying Du ; Charlotte K L. Wong ; Jiadong Chen ; Shuming Duan ; Vincent Deubel ; Bing SunSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2006.
Descripteurs français
- KwdFr :
- Animaux, Cadres ouverts de lecture, Canaux ioniques (génétique), Canaux ioniques (métabolisme), Humains, Lignée cellulaire, Ovocytes (cytologie), Ovocytes (physiologie), Petit ARN interférent (génétique), Petit ARN interférent (métabolisme), Potassium (métabolisme), Protéines recombinantes (génétique), Protéines recombinantes (métabolisme), Protéines virales (génétique), Protéines virales (métabolisme), Réplication virale, Techniques de patch-clamp, Virus du SRAS (génétique), Virus du SRAS (métabolisme), Xenopus laevis.
- MESH :
- cytologie : Ovocytes.
- génétique : Canaux ioniques, Petit ARN interférent, Protéines recombinantes, Protéines virales, Virus du SRAS.
- métabolisme : Canaux ioniques, Petit ARN interférent, Potassium, Protéines recombinantes, Protéines virales, Virus du SRAS.
- physiologie : Ovocytes.
- Animaux, Cadres ouverts de lecture, Humains, Lignée cellulaire, Réplication virale, Techniques de patch-clamp, Xenopus laevis.
English descriptors
- KwdEn :
- Animals, Cell Line, Humans, Ion Channels (genetics), Ion Channels (metabolism), Oocytes (cytology), Oocytes (physiology), Open Reading Frames, Patch-Clamp Techniques, Potassium (metabolism), RNA, Small Interfering (genetics), RNA, Small Interfering (metabolism), Recombinant Proteins (genetics), Recombinant Proteins (metabolism), SARS Virus (genetics), SARS Virus (metabolism), Viral Proteins (genetics), Viral Proteins (metabolism), Virus Replication, Xenopus laevis.
- MESH :
- chemical , genetics : Ion Channels, RNA, Small Interfering, Recombinant Proteins, Viral Proteins.
- chemical , metabolism : Ion Channels, Potassium, RNA, Small Interfering, Recombinant Proteins, Viral Proteins.
- cytology : Oocytes.
- genetics : SARS Virus.
- metabolism : SARS Virus.
- physiology : Oocytes.
- Animals, Cell Line, Humans, Open Reading Frames, Patch-Clamp Techniques, Virus Replication, Xenopus laevis.
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.
Url:
DOI: 10.1073/pnas.0605402103
PubMed: 16894145
Affiliations:
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Le document en format XML
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Wong</name></author><author><name sortKey="Chen, Jiadong" sort="Chen, Jiadong" uniqKey="Chen J" first="Jiadong" last="Chen">Jiadong Chen</name></author><author><name sortKey="Duan, Shuming" sort="Duan, Shuming" uniqKey="Duan S" first="Shuming" last="Duan">Shuming Duan</name></author><author><name sortKey="Deubel, Vincent" sort="Deubel, Vincent" uniqKey="Deubel V" first="Vincent" last="Deubel">Vincent Deubel</name></author><author><name sortKey="Sun, Bing" sort="Sun, Bing" uniqKey="Sun B" first="Bing" last="Sun">Bing Sun</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Humans</term><term>Ion Channels (genetics)</term><term>Ion Channels (metabolism)</term><term>Oocytes (cytology)</term><term>Oocytes (physiology)</term><term>Open Reading Frames</term><term>Patch-Clamp Techniques</term><term>Potassium (metabolism)</term><term>RNA, Small Interfering (genetics)</term><term>RNA, Small Interfering (metabolism)</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (metabolism)</term><term>SARS Virus (genetics)</term><term>SARS Virus (metabolism)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term><term>Virus Replication</term><term>Xenopus laevis</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cadres ouverts de lecture</term><term>Canaux ioniques (génétique)</term><term>Canaux ioniques (métabolisme)</term><term>Humains</term><term>Lignée cellulaire</term><term>Ovocytes (cytologie)</term><term>Ovocytes (physiologie)</term><term>Petit ARN interférent (génétique)</term><term>Petit ARN interférent (métabolisme)</term><term>Potassium (métabolisme)</term><term>Protéines recombinantes (génétique)</term><term>Protéines recombinantes (métabolisme)</term><term>Protéines virales (génétique)</term><term>Protéines virales (métabolisme)</term><term>Réplication virale</term><term>Techniques de patch-clamp</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term><term>Xenopus laevis</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Ion Channels</term><term>RNA, Small Interfering</term><term>Recombinant Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Ion Channels</term><term>Potassium</term><term>RNA, Small Interfering</term><term>Recombinant Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Ovocytes</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Oocytes</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Canaux ioniques</term><term>Petit ARN interférent</term><term>Protéines recombinantes</term><term>Protéines virales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Canaux ioniques</term><term>Petit ARN interférent</term><term>Potassium</term><term>Protéines recombinantes</term><term>Protéines virales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Ovocytes</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Oocytes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Humans</term><term>Open Reading Frames</term><term>Patch-Clamp Techniques</term><term>Virus Replication</term><term>Xenopus laevis</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cadres ouverts de lecture</term><term>Humains</term><term>Lignée cellulaire</term><term>Réplication virale</term><term>Techniques de patch-clamp</term><term>Xenopus laevis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Chen, Jiadong" sort="Chen, Jiadong" uniqKey="Chen J" first="Jiadong" last="Chen">Jiadong Chen</name><name sortKey="Deubel, Vincent" sort="Deubel, Vincent" uniqKey="Deubel V" first="Vincent" last="Deubel">Vincent Deubel</name><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><name sortKey="Duan, Shuming" sort="Duan, Shuming" uniqKey="Duan S" first="Shuming" last="Duan">Shuming Duan</name><name sortKey="Schwarz, Wolfgang" sort="Schwarz, Wolfgang" uniqKey="Schwarz W" first="Wolfgang" last="Schwarz">Wolfgang Schwarz</name><name sortKey="Sun, Bing" sort="Sun, Bing" uniqKey="Sun B" first="Bing" last="Sun">Bing Sun</name><name sortKey="Wong, Charlotte K L" sort="Wong, Charlotte K L" uniqKey="Wong C" first="Charlotte K L" last="Wong">Charlotte K L. Wong</name><name sortKey="Xu, Ke" sort="Xu, Ke" uniqKey="Xu K" first="Ke" last="Xu">Ke Xu</name><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Lu, Wei" sort="Lu, Wei" uniqKey="Lu W" first="Wei" last="Lu">Wei Lu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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