Benchmarking evolutionary tinkering underlying human-viral molecular mimicry shows multiple host pulmonary-arterial peptides mimicked by SARS-CoV-2.
Identifieur interne : 000228 ( Main/Exploration ); précédent : 000227; suivant : 000229Benchmarking evolutionary tinkering underlying human-viral molecular mimicry shows multiple host pulmonary-arterial peptides mimicked by SARS-CoV-2.
Auteurs : A J Venkatakrishnan [États-Unis] ; Nikhil Kayal [États-Unis] ; Praveen Anand [Inde] ; Andrew D. Badley [États-Unis] ; George M. Church [États-Unis] ; Venky Soundararajan [États-Unis]Source :
- Cell death discovery [ 2058-7716 ] ; 2020.
Abstract
The hand of molecular mimicry in shaping SARS-CoV-2 evolution and immune evasion remains to be deciphered. Here, we report 33 distinct 8-mer/9-mer peptides that are identical between SARS-CoV-2 and the human reference proteome. We benchmark this observation against other viral-human 8-mer/9-mer peptide identity, which suggests generally similar extents of molecular mimicry for SARS-CoV-2 and many other human viruses. Interestingly, 20 novel human peptides mimicked by SARS-CoV-2 have not been observed in any previous coronavirus strains (HCoV, SARS-CoV, and MERS). Furthermore, four of the human 8-mer/9-mer peptides mimicked by SARS-CoV-2 map onto HLA-B*40:01, HLA-B*40:02, and HLA-B*35:01 binding peptides from human PAM, ANXA7, PGD, and ALOX5AP proteins. This mimicry of multiple human proteins by SARS-CoV-2 is made salient by single-cell RNA-seq (scRNA-seq) analysis that shows the targeted genes significantly expressed in human lungs and arteries; tissues implicated in COVID-19 pathogenesis. Finally, HLA-A*03 restricted 8-mer peptides are found to be shared broadly by human and coronaviridae helicases in functional hotspots, with potential implications for nucleic acid unwinding upon initial infection. This study presents the first scan of human peptide mimicry by SARS-CoV-2, and via its benchmarking against human-viral mimicry more broadly, presents a computational framework for follow-up studies to assay how evolutionary tinkering may relate to zoonosis and herd immunity.
DOI: 10.1038/s41420-020-00321-y
PubMed: 33024578
PubMed Central: PMC7529588
Affiliations:
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Badley</name><affiliation wicri:level="2"><nlm:affiliation>Department of Infectious Diseases, Mayo Clinic, Rochester, MN USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Department of Infectious Diseases, Mayo Clinic, Rochester</wicri:cityArea></affiliation></author><author><name sortKey="Church, George M" sort="Church, George M" uniqKey="Church G" first="George M" last="Church">George M. Church</name><affiliation wicri:level="1"><nlm:affiliation>Department of Genetics, Harvard Medical School, Boston MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, Harvard Medical School, Boston MA</wicri:regionArea><wicri:noRegion>Boston MA</wicri:noRegion></affiliation></author><author><name sortKey="Soundararajan, Venky" sort="Soundararajan, Venky" uniqKey="Soundararajan V" first="Venky" last="Soundararajan">Venky Soundararajan</name><affiliation wicri:level="2"><nlm:affiliation>nference, Cambridge, MA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>nference, Cambridge</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33024578</idno><idno type="pmid">33024578</idno><idno type="doi">10.1038/s41420-020-00321-y</idno><idno type="pmc">PMC7529588</idno><idno type="wicri:Area/Main/Corpus">000088</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000088</idno><idno type="wicri:Area/Main/Curation">000088</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000088</idno><idno type="wicri:Area/Main/Exploration">000088</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Benchmarking evolutionary tinkering underlying human-viral molecular mimicry shows multiple host pulmonary-arterial peptides mimicked by SARS-CoV-2.</title><author><name sortKey="Venkatakrishnan, A J" sort="Venkatakrishnan, A J" uniqKey="Venkatakrishnan A" first="A J" last="Venkatakrishnan">A J Venkatakrishnan</name><affiliation wicri:level="2"><nlm:affiliation>nference, Cambridge, MA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>nference, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Kayal, Nikhil" sort="Kayal, Nikhil" uniqKey="Kayal N" first="Nikhil" last="Kayal">Nikhil Kayal</name><affiliation wicri:level="2"><nlm:affiliation>nference, Cambridge, MA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>nference, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Anand, Praveen" sort="Anand, Praveen" uniqKey="Anand P" first="Praveen" last="Anand">Praveen Anand</name><affiliation wicri:level="1"><nlm:affiliation>nference Labs, Bangalore, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>nference Labs, Bangalore</wicri:regionArea><wicri:noRegion>Bangalore</wicri:noRegion></affiliation></author><author><name sortKey="Badley, Andrew D" sort="Badley, Andrew D" uniqKey="Badley A" first="Andrew D" last="Badley">Andrew D. Badley</name><affiliation wicri:level="2"><nlm:affiliation>Department of Infectious Diseases, Mayo Clinic, Rochester, MN USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Department of Infectious Diseases, Mayo Clinic, Rochester</wicri:cityArea></affiliation></author><author><name sortKey="Church, George M" sort="Church, George M" uniqKey="Church G" first="George M" last="Church">George M. Church</name><affiliation wicri:level="1"><nlm:affiliation>Department of Genetics, Harvard Medical School, Boston MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, Harvard Medical School, Boston MA</wicri:regionArea><wicri:noRegion>Boston MA</wicri:noRegion></affiliation></author><author><name sortKey="Soundararajan, Venky" sort="Soundararajan, Venky" uniqKey="Soundararajan V" first="Venky" last="Soundararajan">Venky Soundararajan</name><affiliation wicri:level="2"><nlm:affiliation>nference, Cambridge, MA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>nference, Cambridge</wicri:cityArea></affiliation></author></analytic><series><title level="j">Cell death discovery</title><idno type="ISSN">2058-7716</idno><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 hand of molecular mimicry in shaping SARS-CoV-2 evolution and immune evasion remains to be deciphered. Here, we report 33 distinct 8-mer/9-mer peptides that are identical between SARS-CoV-2 and the human reference proteome. We benchmark this observation against other viral-human 8-mer/9-mer peptide identity, which suggests generally similar extents of molecular mimicry for SARS-CoV-2 and many other human viruses. Interestingly, 20 novel human peptides mimicked by SARS-CoV-2 have not been observed in any previous coronavirus strains (HCoV, SARS-CoV, and MERS). Furthermore, four of the human 8-mer/9-mer peptides mimicked by SARS-CoV-2 map onto HLA-B*40:01, HLA-B*40:02, and HLA-B*35:01 binding peptides from human PAM, ANXA7, PGD, and ALOX5AP proteins. This mimicry of multiple human proteins by SARS-CoV-2 is made salient by single-cell RNA-seq (scRNA-seq) analysis that shows the targeted genes significantly expressed in human lungs and arteries; tissues implicated in COVID-19 pathogenesis. Finally, HLA-A*03 restricted 8-mer peptides are found to be shared broadly by human and coronaviridae helicases in functional hotspots, with potential implications for nucleic acid unwinding upon initial infection. This study presents the first scan of human peptide mimicry by SARS-CoV-2, and via its benchmarking against human-viral mimicry more broadly, presents a computational framework for follow-up studies to assay how evolutionary tinkering may relate to zoonosis and herd immunity.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33024578</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>09</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2058-7716</ISSN><JournalIssue CitedMedium="Print"><Volume>6</Volume><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Cell death discovery</Title><ISOAbbreviation>Cell Death Discov</ISOAbbreviation></Journal><ArticleTitle>Benchmarking evolutionary tinkering underlying human-viral molecular mimicry shows multiple host pulmonary-arterial peptides mimicked by SARS-CoV-2.</ArticleTitle><Pagination><MedlinePgn>96</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41420-020-00321-y</ELocationID><Abstract><AbstractText>The hand of molecular mimicry in shaping SARS-CoV-2 evolution and immune evasion remains to be deciphered. Here, we report 33 distinct 8-mer/9-mer peptides that are identical between SARS-CoV-2 and the human reference proteome. We benchmark this observation against other viral-human 8-mer/9-mer peptide identity, which suggests generally similar extents of molecular mimicry for SARS-CoV-2 and many other human viruses. Interestingly, 20 novel human peptides mimicked by SARS-CoV-2 have not been observed in any previous coronavirus strains (HCoV, SARS-CoV, and MERS). Furthermore, four of the human 8-mer/9-mer peptides mimicked by SARS-CoV-2 map onto HLA-B*40:01, HLA-B*40:02, and HLA-B*35:01 binding peptides from human PAM, ANXA7, PGD, and ALOX5AP proteins. This mimicry of multiple human proteins by SARS-CoV-2 is made salient by single-cell RNA-seq (scRNA-seq) analysis that shows the targeted genes significantly expressed in human lungs and arteries; tissues implicated in COVID-19 pathogenesis. Finally, HLA-A*03 restricted 8-mer peptides are found to be shared broadly by human and coronaviridae helicases in functional hotspots, with potential implications for nucleic acid unwinding upon initial infection. This study presents the first scan of human peptide mimicry by SARS-CoV-2, and via its benchmarking against human-viral mimicry more broadly, presents a computational framework for follow-up studies to assay how evolutionary tinkering may relate to zoonosis and herd immunity.</AbstractText><CopyrightInformation>© The Author(s) 2020.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Venkatakrishnan</LastName><ForeName>A J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>nference, Cambridge, MA USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kayal</LastName><ForeName>Nikhil</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>nference, Cambridge, MA USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anand</LastName><ForeName>Praveen</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>nference Labs, Bangalore, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Badley</LastName><ForeName>Andrew D</ForeName><Initials>AD</Initials><Identifier Source="ORCID">0000-0001-7796-7680</Identifier><AffiliationInfo><Affiliation>Department of Infectious Diseases, Mayo Clinic, Rochester, MN USA.</Affiliation><Identifier Source="GRID">grid.66875.3a</Identifier><Identifier Source="ISNI">0000 0004 0459 167X</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Church</LastName><ForeName>George M</ForeName><Initials>GM</Initials><AffiliationInfo><Affiliation>Department of Genetics, Harvard Medical School, Boston MA, USA.</Affiliation><Identifier Source="GRID">grid.38142.3c</Identifier><Identifier Source="ISNI">000000041936754X</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Soundararajan</LastName><ForeName>Venky</ForeName><Initials>V</Initials><Identifier Source="ORCID">0000-0001-7434-9211</Identifier><AffiliationInfo><Affiliation>nference, Cambridge, MA USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>10</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cell Death Discov</MedlineTA><NlmUniqueID>101665035</NlmUniqueID><ISSNLinking>2058-7716</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Environmental microbiology</Keyword><Keyword MajorTopicYN="N">Proteomics</Keyword></KeywordList><CoiStatement>Conflict of interestThe authors declare that they have no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>08</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>09</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>10</Month><Day>7</Day><Hour>5</Hour><Minute>50</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>10</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>10</Month><Day>8</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33024578</ArticleId><ArticleId IdType="doi">10.1038/s41420-020-00321-y</ArticleId><ArticleId IdType="pii">321</ArticleId><ArticleId IdType="pmc">PMC7529588</ArticleId></ArticleIdList><pmc-dir>pmcsd</pmc-dir>
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sort="Badley, Andrew D" uniqKey="Badley A" first="Andrew D" last="Badley">Andrew D. Badley</name><name sortKey="Church, George M" sort="Church, George M" uniqKey="Church G" first="George M" last="Church">George M. Church</name><name sortKey="Kayal, Nikhil" sort="Kayal, Nikhil" uniqKey="Kayal N" first="Nikhil" last="Kayal">Nikhil Kayal</name><name sortKey="Soundararajan, Venky" sort="Soundararajan, Venky" uniqKey="Soundararajan V" first="Venky" last="Soundararajan">Venky Soundararajan</name></country><country name="Inde"><noRegion><name sortKey="Anand, Praveen" sort="Anand, Praveen" uniqKey="Anand P" first="Praveen" last="Anand">Praveen Anand</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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