The D614G mutation in the SARS-CoV2 Spike protein increases infectivity in an ACE2 receptor dependent manner.
Identifieur interne : 000094 ( Main/Exploration ); précédent : 000093; suivant : 000095The D614G mutation in the SARS-CoV2 Spike protein increases infectivity in an ACE2 receptor dependent manner.
Auteurs : Junko Ogawa ; Wei Zhu [États-Unis] ; Nina Tonnu ; Oded Singer [Israël] ; Tony Hunter ; Amy L. Ryan [États-Unis] ; Gerald M. PaoSource :
- bioRxiv : the preprint server for biology ; 2020.
Abstract
The SARS-CoV2 coronavirus responsible for the current COVID19 pandemic has been reported to have a relatively low mutation rate. Nevertheless, a few prevalent variants have arisen that give the appearance of undergoing positive selection as they are becoming increasingly widespread over time. Most prominent among these is the D614G amino acid substitution in the SARS-CoV2 Spike protein, which mediates viral entry. The D614G substitution, however, is in linkage disequilibrium with the ORF1b P314L mutation where both mutations almost invariably co-occur, making functional inferences problematic. In addition, the possibility of repeated new introductions of the mutant strain does not allow one to distinguish between a founder effect and an intrinsic genetic property of the virus. Here, we synthesized and expressed the WT and D614G variant SARS-Cov2 Spike protein, and report that using a SARS-CoV2 Spike protein pseudotyped lentiviral vector we observe that the D614G variant Spike has >1/2 log10 increased infectivity in human cells expressing the human ACE2 protein as the viral receptor. The increased binding/fusion activity of the D614G Spike protein was corroborated in a cell fusion assay using Spike and ACE2 proteins expressed in different cells. These results are consistent with the possibility that the Spike D614G mutant increases the infectivity of SARS-CoV2.
DOI: 10.1101/2020.07.21.214932
PubMed: 32743569
PubMed Central: PMC7386486
Affiliations:
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Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</nlm:affiliation><wicri:noCountry code="no comma">Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</wicri:noCountry></affiliation></author><author><name sortKey="Zhu, Wei" sort="Zhu, Wei" uniqKey="Zhu W" first="Wei" last="Zhu">Wei Zhu</name><affiliation wicri:level="2"><nlm:affiliation>University of California, San Diego. Department of Biology 9500 Gilman Drive, La Jolla CA 92093.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>University of California, San Diego. Department of Biology 9500 Gilman Drive</wicri:cityArea></affiliation></author><author><name sortKey="Tonnu, Nina" sort="Tonnu, Nina" uniqKey="Tonnu N" first="Nina" last="Tonnu">Nina Tonnu</name><affiliation><nlm:affiliation>Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</nlm:affiliation><wicri:noCountry code="no comma">Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</wicri:noCountry></affiliation></author><author><name sortKey="Singer, Oded" sort="Singer, Oded" uniqKey="Singer O" first="Oded" last="Singer">Oded Singer</name><affiliation wicri:level="1"><nlm:affiliation>Life Sciences Core Facilities, Weizmann Institute of Science, 7610001 Rehovot, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Life Sciences Core Facilities, Weizmann Institute of Science, 7610001 Rehovot</wicri:regionArea><wicri:noRegion>7610001 Rehovot</wicri:noRegion></affiliation></author><author><name sortKey="Hunter, Tony" sort="Hunter, Tony" uniqKey="Hunter T" first="Tony" last="Hunter">Tony Hunter</name><affiliation><nlm:affiliation>Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</nlm:affiliation><wicri:noCountry code="no comma">Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</wicri:noCountry></affiliation></author><author><name sortKey="Ryan, Amy L" sort="Ryan, Amy L" uniqKey="Ryan A" first="Amy L" last="Ryan">Amy L. Ryan</name><affiliation wicri:level="2"><nlm:affiliation>Hastings Center for Pulmonary Research, Department of Pulmonary, Critical Care and Sleep Medicine, USC Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Hastings Center for Pulmonary Research, Department of Pulmonary, Critical Care and Sleep Medicine, USC Keck School of Medicine, 2011 Zonal Avenue, Los Angeles</wicri:cityArea></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Stem Cell and Regenerative Medicine, University of Southern California, 1405 San Pablo Street, Los Angeles, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Stem Cell and Regenerative Medicine, University of Southern California, 1405 San Pablo Street, Los Angeles, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Los Angeles</settlement></placeName><orgName type="university">Université de Californie du Sud</orgName></affiliation></author><author><name sortKey="Pao, Gerald M" sort="Pao, Gerald M" uniqKey="Pao G" first="Gerald M" last="Pao">Gerald M. Pao</name><affiliation><nlm:affiliation>Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</nlm:affiliation><wicri:noCountry code="no comma">Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</wicri:noCountry></affiliation></author></analytic><series><title level="j">bioRxiv : the preprint server for biology</title><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The SARS-CoV2 coronavirus responsible for the current COVID19 pandemic has been reported to have a relatively low mutation rate. Nevertheless, a few prevalent variants have arisen that give the appearance of undergoing positive selection as they are becoming increasingly widespread over time. Most prominent among these is the D614G amino acid substitution in the SARS-CoV2 Spike protein, which mediates viral entry. The D614G substitution, however, is in linkage disequilibrium with the ORF1b P314L mutation where both mutations almost invariably co-occur, making functional inferences problematic. In addition, the possibility of repeated new introductions of the mutant strain does not allow one to distinguish between a founder effect and an intrinsic genetic property of the virus. Here, we synthesized and expressed the WT and D614G variant SARS-Cov2 Spike protein, and report that using a SARS-CoV2 Spike protein pseudotyped lentiviral vector we observe that the D614G variant Spike has >1/2 log<sub>10</sub> increased infectivity in human cells expressing the human ACE2 protein as the viral receptor. The increased binding/fusion activity of the D614G Spike protein was corroborated in a cell fusion assay using Spike and ACE2 proteins expressed in different cells. These results are consistent with the possibility that the Spike D614G mutant increases the infectivity of SARS-CoV2.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32743569</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>28</Day></DateRevised><Article PubModel="Electronic"><Journal><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Jul</Month><Day>22</Day></PubDate></JournalIssue><Title>bioRxiv : the preprint server for biology</Title><ISOAbbreviation>bioRxiv</ISOAbbreviation></Journal><ArticleTitle>The D614G mutation in the SARS-CoV2 Spike protein increases infectivity in an ACE2 receptor dependent manner.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">2020.07.21.214932</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1101/2020.07.21.214932</ELocationID><Abstract><AbstractText>The SARS-CoV2 coronavirus responsible for the current COVID19 pandemic has been reported to have a relatively low mutation rate. Nevertheless, a few prevalent variants have arisen that give the appearance of undergoing positive selection as they are becoming increasingly widespread over time. Most prominent among these is the D614G amino acid substitution in the SARS-CoV2 Spike protein, which mediates viral entry. The D614G substitution, however, is in linkage disequilibrium with the ORF1b P314L mutation where both mutations almost invariably co-occur, making functional inferences problematic. In addition, the possibility of repeated new introductions of the mutant strain does not allow one to distinguish between a founder effect and an intrinsic genetic property of the virus. Here, we synthesized and expressed the WT and D614G variant SARS-Cov2 Spike protein, and report that using a SARS-CoV2 Spike protein pseudotyped lentiviral vector we observe that the D614G variant Spike has >1/2 log<sub>10</sub> increased infectivity in human cells expressing the human ACE2 protein as the viral receptor. The increased binding/fusion activity of the D614G Spike protein was corroborated in a cell fusion assay using Spike and ACE2 proteins expressed in different cells. These results are consistent with the possibility that the Spike D614G mutant increases the infectivity of SARS-CoV2.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ogawa</LastName><ForeName>Junko</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>University of California, San Diego. Department of Biology 9500 Gilman Drive, La Jolla CA 92093.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tonnu</LastName><ForeName>Nina</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Singer</LastName><ForeName>Oded</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Life Sciences Core Facilities, Weizmann Institute of Science, 7610001 Rehovot, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hunter</LastName><ForeName>Tony</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ryan</LastName><ForeName>Amy L</ForeName><Initials>AL</Initials><AffiliationInfo><Affiliation>Hastings Center for Pulmonary Research, Department of Pulmonary, Critical Care and Sleep Medicine, USC Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Stem Cell and Regenerative Medicine, University of Southern California, 1405 San Pablo Street, Los Angeles, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pao</LastName><ForeName>Gerald M</ForeName><Initials>GM</Initials><AffiliationInfo><Affiliation>Salk Institute for Biological Studies. Molecular and Cellular Biology Laboratory 4 10010 North Torrey Pines Rd. La Jolla CA 92037.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D000076942">Preprint</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>07</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>bioRxiv</MedlineTA><NlmUniqueID>101680187</NlmUniqueID></MedlineJournalInfo></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>8</Month><Day>4</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32743569</ArticleId><ArticleId IdType="doi">10.1101/2020.07.21.214932</ArticleId><ArticleId IdType="pmc">PMC7386486</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Nature. 2020 Mar;579(7798):270-273</Citation><ArticleIdList><ArticleId IdType="pubmed">32015507</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Protoc. 2006;1(1):241-5</Citation><ArticleIdList><ArticleId IdType="pubmed">17406239</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5871-6</Citation><ArticleIdList><ArticleId IdType="pubmed">19321428</ArticleId></ArticleIdList></Reference><Reference><Citation>Bioinformatics. 2018 Dec 1;34(23):4121-4123</Citation><ArticleIdList><ArticleId IdType="pubmed">29790939</ArticleId></ArticleIdList></Reference><Reference><Citation>Euro Surveill. 2020 Apr;25(13):</Citation><ArticleIdList><ArticleId IdType="pubmed">32265007</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Commun. 2020 Mar 27;11(1):1620</Citation><ArticleIdList><ArticleId IdType="pubmed">32221306</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2020 Apr 16;181(2):271-280.e8</Citation><ArticleIdList><ArticleId IdType="pubmed">32142651</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2020 Mar;579(7798):265-269</Citation><ArticleIdList><ArticleId IdType="pubmed">32015508</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Israël</li><li>États-Unis</li></country><region><li>Californie</li></region><settlement><li>Los Angeles</li></settlement><orgName><li>Université de Californie du Sud</li></orgName></list><tree><noCountry><name sortKey="Hunter, Tony" sort="Hunter, Tony" uniqKey="Hunter T" first="Tony" last="Hunter">Tony Hunter</name><name sortKey="Ogawa, Junko" sort="Ogawa, Junko" uniqKey="Ogawa J" first="Junko" last="Ogawa">Junko Ogawa</name><name sortKey="Pao, Gerald M" sort="Pao, Gerald M" uniqKey="Pao G" first="Gerald M" last="Pao">Gerald M. Pao</name><name sortKey="Tonnu, Nina" sort="Tonnu, Nina" uniqKey="Tonnu N" first="Nina" last="Tonnu">Nina Tonnu</name></noCountry><country name="États-Unis"><region name="Californie"><name sortKey="Zhu, Wei" sort="Zhu, Wei" uniqKey="Zhu W" first="Wei" last="Zhu">Wei Zhu</name></region><name sortKey="Ryan, Amy L" sort="Ryan, Amy L" uniqKey="Ryan A" first="Amy L" last="Ryan">Amy L. Ryan</name><name sortKey="Ryan, Amy L" sort="Ryan, Amy L" uniqKey="Ryan A" first="Amy L" last="Ryan">Amy L. Ryan</name></country><country name="Israël"><noRegion><name sortKey="Singer, Oded" sort="Singer, Oded" uniqKey="Singer O" first="Oded" last="Singer">Oded Singer</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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