Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
Identifieur interne : 000494 ( an2020/Analysis ); précédent : 000493; suivant : 000495Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
Auteurs : Arinjay Banerjee [Canada] ; Xi Zhang [Canada] ; Alyssa Yip [Canada] ; Katharina S. Schulz [Canada] ; Aaron T. Irving [Singapour] ; Dawn Bowdish [Canada] ; Brian Golding [Canada] ; Lin-Fa Wang [Singapour] ; Karen Mossman [Canada]Source :
- iScience [ 2589-0042 ] ; 2020.
Abstract
Compared with other mammals, bats harbor more zoonotic viruses per species and do not demonstrate signs of disease on infection with these viruses. To counteract infections with viruses, bats have evolved enhanced mechanisms to limit virus replication and immunopathology. However, molecular and cellular drivers of antiviral responses in bats largely remain an enigma. In this study, we demonstrate that a serine residue in IRF3 is positively selected for in multiple bat species. IRF3 is a central regulator of innate antiviral responses in mammals. Replacing the serine residue in bat IRF3 with the human leucine residue decreased antiviral protection in bat cells, whereas the addition of this serine residue in human IRF3 significantly enhanced antiviral protection in human cells. Our study provides genetic and functional evidence for enhanced IRF3-mediated antiviral responses in bats and adds support to speculations that bats have positively selected for multiple adaptations in their antiviral immune responses.
Url:
DOI: 10.1016/j.isci.2020.100958
PubMed: 32179480
PubMed Central: 7075978
Affiliations:
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PMC:7075978Le document en format XML
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xml:lang="fr">Canada</country><wicri:regionArea>Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Zhang, Xi" sort="Zhang, Xi" uniqKey="Zhang X" first="Xi" last="Zhang">Xi Zhang</name><affiliation wicri:level="4"><nlm:aff id="aff2">Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, McMaster University, Hamilton, ON L8S 4K1</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Yip, Alyssa" sort="Yip, Alyssa" uniqKey="Yip A" first="Alyssa" last="Yip">Alyssa Yip</name><affiliation wicri:level="4"><nlm:aff id="aff1">Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Schulz, Katharina S" sort="Schulz, Katharina S" uniqKey="Schulz K" first="Katharina S." last="Schulz">Katharina S. Schulz</name><affiliation wicri:level="4"><nlm:aff id="aff1">Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Irving, Aaron T" sort="Irving, Aaron T" uniqKey="Irving A" first="Aaron T." last="Irving">Aaron T. Irving</name><affiliation wicri:level="1"><nlm:aff id="aff3">Programme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore 169857, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Programme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore 169857</wicri:regionArea><wicri:noRegion>Singapore 169857</wicri:noRegion></affiliation></author><author><name sortKey="Bowdish, Dawn" sort="Bowdish, Dawn" uniqKey="Bowdish D" first="Dawn" last="Bowdish">Dawn Bowdish</name><affiliation wicri:level="4"><nlm:aff id="aff1">Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Golding, Brian" sort="Golding, Brian" uniqKey="Golding B" first="Brian" last="Golding">Brian Golding</name><affiliation wicri:level="4"><nlm:aff id="aff2">Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, McMaster University, Hamilton, ON L8S 4K1</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name><affiliation wicri:level="1"><nlm:aff id="aff3">Programme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore 169857, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Programme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore 169857</wicri:regionArea><wicri:noRegion>Singapore 169857</wicri:noRegion></affiliation></author><author><name sortKey="Mossman, Karen" sort="Mossman, Karen" uniqKey="Mossman K" first="Karen" last="Mossman">Karen Mossman</name><affiliation wicri:level="4"><nlm:aff id="aff1">Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">iScience</title><idno type="ISSN">2589-0042</idno><idno type="eISSN">2589-0042</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>Compared with other mammals, bats harbor more zoonotic viruses per species and do not demonstrate signs of disease on infection with these viruses. To counteract infections with viruses, bats have evolved enhanced mechanisms to limit virus replication and immunopathology. However, molecular and cellular drivers of antiviral responses in bats largely remain an enigma. In this study, we demonstrate that a serine residue in IRF3 is positively selected for in multiple bat species. IRF3 is a central regulator of innate antiviral responses in mammals. Replacing the serine residue in bat IRF3 with the human leucine residue decreased antiviral protection in bat cells, whereas the addition of this serine residue in human IRF3 significantly enhanced antiviral protection in human cells. Our study provides genetic and functional evidence for enhanced IRF3-mediated antiviral responses in bats and adds support to speculations that bats have positively selected for multiple adaptations in their antiviral immune responses.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ahn, M" uniqKey="Ahn M">M. Ahn</name></author><author><name sortKey="Anderson, D E" uniqKey="Anderson D">D.E. Anderson</name></author><author><name sortKey="Zhang, Q" uniqKey="Zhang Q">Q. Zhang</name></author><author><name sortKey="Tan, C W" uniqKey="Tan C">C.W. Tan</name></author><author><name sortKey="Lim, B L" uniqKey="Lim B">B.L. Lim</name></author><author><name sortKey="Luko, K" uniqKey="Luko K">K. Luko</name></author><author><name sortKey="Wen, M" uniqKey="Wen M">M. Wen</name></author><author><name sortKey="Chia, W N" uniqKey="Chia W">W.N. Chia</name></author><author><name sortKey="Mani, S" uniqKey="Mani S">S. 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Tachedjian</name></author><author><name sortKey="Wynne, J W" uniqKey="Wynne J">J.W. Wynne</name></author><author><name sortKey="Boyd, V" uniqKey="Boyd V">V. Boyd</name></author><author><name sortKey="Cui, J" uniqKey="Cui J">J. Cui</name></author><author><name sortKey="Smith, I" uniqKey="Smith I">I. Smith</name></author><author><name sortKey="Cowled, C" uniqKey="Cowled C">C. Cowled</name></author><author><name sortKey="Ng, J H" uniqKey="Ng J">J.H. Ng</name></author><author><name sortKey="Mok, L" uniqKey="Mok L">L. Mok</name></author><author><name sortKey="Michalski, W P" uniqKey="Michalski W">W.P. Michalski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, P" uniqKey="Zhou P">P. Zhou</name></author><author><name sortKey="Yang, X L" uniqKey="Yang X">X.L. yang</name></author><author><name sortKey="Wang, X G" uniqKey="Wang X">X.G. Wang</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B. Hu</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Si, H R" uniqKey="Si H">H.R. Si</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y. Zhu</name></author><author><name sortKey="Li, B" uniqKey="Li B">B. Li</name></author><author><name sortKey="Huang, C L" uniqKey="Huang C">C.L. Huang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>Singapour</li></country><region><li>Ontario</li></region><settlement><li>Hamilton (Ontario)</li></settlement><orgName><li>Université McMaster</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Banerjee, Arinjay" sort="Banerjee, Arinjay" uniqKey="Banerjee A" first="Arinjay" last="Banerjee">Arinjay Banerjee</name></region><name sortKey="Bowdish, Dawn" sort="Bowdish, Dawn" uniqKey="Bowdish D" first="Dawn" last="Bowdish">Dawn Bowdish</name><name sortKey="Golding, Brian" sort="Golding, Brian" uniqKey="Golding B" first="Brian" last="Golding">Brian Golding</name><name sortKey="Mossman, Karen" sort="Mossman, Karen" uniqKey="Mossman K" first="Karen" last="Mossman">Karen Mossman</name><name sortKey="Schulz, Katharina S" sort="Schulz, Katharina S" uniqKey="Schulz K" first="Katharina S." last="Schulz">Katharina S. Schulz</name><name sortKey="Yip, Alyssa" sort="Yip, Alyssa" uniqKey="Yip A" first="Alyssa" last="Yip">Alyssa Yip</name><name sortKey="Zhang, Xi" sort="Zhang, Xi" uniqKey="Zhang X" first="Xi" last="Zhang">Xi Zhang</name></country><country name="Singapour"><noRegion><name sortKey="Irving, Aaron T" sort="Irving, Aaron T" uniqKey="Irving A" first="Aaron T." last="Irving">Aaron T. Irving</name></noRegion><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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