Two-amino acids change in the nsp4 of SARS coronavirus abolishes viral replication
Identifieur interne : 000D46 ( Main/Exploration ); précédent : 000D45; suivant : 000D47Two-amino acids change in the nsp4 of SARS coronavirus abolishes viral replication
Auteurs : Yusuke Sakai [Japon] ; Kengo Kawachi [Japon] ; Yutaka Terada [Japon] ; Hiroko Omori [Japon] ; Yoshiharu Matsuura [Japon] ; Wataru Kamitani [Japon]Source :
- Virology [ 0042-6822 ] ; 2017.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Viral Nonstructural Proteins.
- genetics : SARS Virus.
- physiology : SARS Virus.
- Amino Acid Substitution, DNA Mutational Analysis, Protein Interaction Mapping, Virus Replication.
Abstract
Infection with coronavirus rearranges the host cell membrane to assemble a replication/transcription complex in which replication of the viral genome and transcription of viral mRNA occur. Although coexistence of nsp3 and nsp4 is known to cause membrane rearrangement, the mechanisms underlying the interaction of these two proteins remain unclear. We demonstrated that binding of nsp4 with nsp3 is essential for membrane rearrangement and identified amino acid residues in nsp4 responsible for the interaction with nsp3. In addition, we revealed that the nsp3-nsp4 interaction is not sufficient to induce membrane rearrangement, suggesting the participation of other factors such as host proteins. Finally, we showed that loss of the nsp3-nsp4 interaction eliminated viral replication by using an infectious cDNA clone and replicon system of SARS-CoV. These findings provide clues to the mechanism of the replication/transcription complex assembly of SARS-CoV and could reveal an antiviral target for the treatment of betacoronavirus infection.
Url:
DOI: 10.1016/j.virol.2017.07.019
PubMed: 28738245
PubMed Central: 7111695
Affiliations:
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replication</title><author><name sortKey="Sakai, Yusuke" sort="Sakai, Yusuke" uniqKey="Sakai Y" first="Yusuke" last="Sakai">Yusuke Sakai</name><affiliation wicri:level="1"><nlm:aff id="aff0005">Laboratory of Clinical Research on Infectious Diseases, Osaka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Clinical Research on Infectious Diseases, Osaka</wicri:regionArea><wicri:noRegion>Osaka</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0020">Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi</wicri:regionArea><wicri:noRegion>Yamaguchi</wicri:noRegion></affiliation></author><author><name sortKey="Kawachi, Kengo" sort="Kawachi, Kengo" uniqKey="Kawachi K" first="Kengo" last="Kawachi">Kengo Kawachi</name><affiliation wicri:level="1"><nlm:aff id="aff0005">Laboratory of Clinical Research on Infectious Diseases, Osaka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Clinical Research on Infectious Diseases, Osaka</wicri:regionArea><wicri:noRegion>Osaka</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0010">Department of Molecular Virology, Osaka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Osaka</wicri:regionArea><wicri:noRegion>Osaka</wicri:noRegion></affiliation></author><author><name sortKey="Terada, Yutaka" sort="Terada, Yutaka" uniqKey="Terada Y" first="Yutaka" last="Terada">Yutaka Terada</name><affiliation wicri:level="1"><nlm:aff id="aff0005">Laboratory of Clinical Research on Infectious Diseases, Osaka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Clinical Research on Infectious Diseases, 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Osaka</wicri:regionArea><wicri:noRegion>Osaka</wicri:noRegion></affiliation></author><author><name sortKey="Kamitani, Wataru" sort="Kamitani, Wataru" uniqKey="Kamitani W" first="Wataru" last="Kamitani">Wataru Kamitani</name><affiliation wicri:level="1"><nlm:aff id="aff0005">Laboratory of Clinical Research on Infectious Diseases, Osaka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Clinical Research on Infectious Diseases, Osaka</wicri:regionArea><wicri:noRegion>Osaka</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff0025">Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki 305-0843, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki 305-0843</wicri:regionArea><wicri:noRegion>Ibaraki 305-0843</wicri:noRegion></affiliation></author></analytic><series><title level="j">Virology</title><idno type="ISSN">0042-6822</idno><idno type="eISSN">1096-0341</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution</term><term>DNA Mutational Analysis</term><term>Protein Interaction Mapping</term><term>SARS Virus (genetics)</term><term>SARS Virus (physiology)</term><term>Viral Nonstructural Proteins (genetics)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de mutations d'ADN</term><term>Cartographie d'interactions entre protéines</term><term>Protéines virales non structurales (génétique)</term><term>Réplication virale</term><term>Substitution d'acide aminé</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines virales non structurales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term><term>DNA Mutational Analysis</term><term>Protein Interaction Mapping</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de mutations d'ADN</term><term>Cartographie d'interactions entre protéines</term><term>Réplication virale</term><term>Substitution d'acide aminé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Infection with coronavirus rearranges the host cell membrane to assemble a replication/transcription complex in which replication of the viral genome and transcription of viral mRNA occur. Although coexistence of nsp3 and nsp4 is known to cause membrane rearrangement, the mechanisms underlying the interaction of these two proteins remain unclear. We demonstrated that binding of nsp4 with nsp3 is essential for membrane rearrangement and identified amino acid residues in nsp4 responsible for the interaction with nsp3. In addition, we revealed that the nsp3-nsp4 interaction is not sufficient to induce membrane rearrangement, suggesting the participation of other factors such as host proteins. Finally, we showed that loss of the nsp3-nsp4 interaction eliminated viral replication by using an infectious cDNA clone and replicon system of SARS-CoV. These findings provide clues to the mechanism of the replication/transcription complex assembly of SARS-CoV and could reveal an antiviral target for the treatment of betacoronavirus infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Almazan, F" uniqKey="Almazan F">F. 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Fouchier</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Sakai, Yusuke" sort="Sakai, Yusuke" uniqKey="Sakai Y" first="Yusuke" last="Sakai">Yusuke Sakai</name></noRegion><name sortKey="Kamitani, Wataru" sort="Kamitani, Wataru" uniqKey="Kamitani W" first="Wataru" last="Kamitani">Wataru Kamitani</name><name sortKey="Kamitani, Wataru" sort="Kamitani, Wataru" uniqKey="Kamitani W" first="Wataru" last="Kamitani">Wataru Kamitani</name><name sortKey="Kawachi, Kengo" sort="Kawachi, Kengo" uniqKey="Kawachi K" first="Kengo" last="Kawachi">Kengo Kawachi</name><name sortKey="Kawachi, Kengo" sort="Kawachi, Kengo" uniqKey="Kawachi K" first="Kengo" last="Kawachi">Kengo Kawachi</name><name sortKey="Matsuura, Yoshiharu" sort="Matsuura, Yoshiharu" uniqKey="Matsuura Y" first="Yoshiharu" last="Matsuura">Yoshiharu Matsuura</name><name sortKey="Omori, Hiroko" sort="Omori, Hiroko" uniqKey="Omori H" first="Hiroko" last="Omori">Hiroko Omori</name><name sortKey="Sakai, Yusuke" sort="Sakai, Yusuke" uniqKey="Sakai Y" first="Yusuke" last="Sakai">Yusuke Sakai</name><name sortKey="Terada, Yutaka" sort="Terada, Yutaka" uniqKey="Terada Y" first="Yutaka" last="Terada">Yutaka Terada</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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