Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection

Summary: 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...

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Main Authors: Arinjay Banerjee, Xi Zhang, Alyssa Yip, Katharina S. Schulz, Aaron T. Irving, Dawn Bowdish, Brian Golding, Lin-Fa Wang, Karen Mossman
Format: Article
Language:English
Published: Elsevier 2020-03-01
Series:iScience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220301425
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author Arinjay Banerjee
Xi Zhang
Alyssa Yip
Katharina S. Schulz
Aaron T. Irving
Dawn Bowdish
Brian Golding
Lin-Fa Wang
Karen Mossman
author_facet Arinjay Banerjee
Xi Zhang
Alyssa Yip
Katharina S. Schulz
Aaron T. Irving
Dawn Bowdish
Brian Golding
Lin-Fa Wang
Karen Mossman
author_sort Arinjay Banerjee
collection DOAJ
description Summary: 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. : Biological Sciences; Immunology; Evolutionary Biology Subject Areas: Biological Sciences, Immunology, Evolutionary Biology
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spelling doaj.art-21980b4a25b94f8086c79d06400786ed2022-12-21T18:53:52ZengElsevieriScience2589-00422020-03-01233Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral ProtectionArinjay Banerjee0Xi Zhang1Alyssa Yip2Katharina S. Schulz3Aaron T. Irving4Dawn Bowdish5Brian Golding6Lin-Fa Wang7Karen Mossman8Michael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Biology, McMaster University, Hamilton, ON L8S 4K1, CanadaMichael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaMichael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaProgramme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore 169857, SingaporeMichael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Biology, McMaster University, Hamilton, ON L8S 4K1, CanadaProgramme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore 169857, SingaporeMichael DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada; Corresponding authorSummary: 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. : Biological Sciences; Immunology; Evolutionary Biology Subject Areas: Biological Sciences, Immunology, Evolutionary Biologyhttp://www.sciencedirect.com/science/article/pii/S2589004220301425
spellingShingle Arinjay Banerjee
Xi Zhang
Alyssa Yip
Katharina S. Schulz
Aaron T. Irving
Dawn Bowdish
Brian Golding
Lin-Fa Wang
Karen Mossman
Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
iScience
title Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
title_full Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
title_fullStr Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
title_full_unstemmed Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
title_short Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
title_sort positive selection of a serine residue in bat irf3 confers enhanced antiviral protection
url http://www.sciencedirect.com/science/article/pii/S2589004220301425
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