Antivirals; Defence systems; DNA virus; Functional testing; Genomics; Innate defense; Pathogenics; Positive selection; Protein kinase; RNA virus; Multidisciplinary; Evolution
Abstract :
[en] Several bat species act as asymptomatic reservoirs for many viruses that are highly pathogenic in other mammals. Here, we have characterized the functional diversification of the protein kinase R (PKR), a major antiviral innate defense system. Our data indicate that PKR has evolved under positive selection and has undergone repeated genomic duplications in bats in contrast to all studied mammals that have a single copy of the gene. Functional testing of the relationship between PKR and poxvirus antagonists revealed how an evolutionary conflict with ancient pathogenic poxviruses has shaped a specific bat host-virus interface. We determined that duplicated PKRs of the Myotis species have undergone genetic diversification, allowing them to collectively escape from and enhance the control of DNA and RNA viruses. These findings suggest that viral-driven adaptations in PKR contribute to modern virus-bat interactions and may account for bat-specific immunity.
Disciplines :
Microbiology
Author, co-author :
Jacquet, Stéphanie ; Laboratoire de Biométrie et Biologie Evolutive (LBBE), UMR 5558, UCBL1, CNRS, Lyon, France ; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France
Culbertson, Michelle ; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA
Zhang, Chi ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA 95616, USA
El Filali, Adil ; Laboratoire de Biométrie et Biologie Evolutive (LBBE), UMR 5558, UCBL1, CNRS, Lyon, France
de la Myre Mory, Clément ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie ; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France
Pons, Jean-Baptiste; Laboratoire de Biométrie et Biologie Evolutive (LBBE), UMR 5558, UCBL1, CNRS, Lyon, France
Filippi-Codaccioni, Ondine; Laboratoire de Biométrie et Biologie Evolutive (LBBE), UMR 5558, UCBL1, CNRS, Lyon, France
Lauterbur, M Elise ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA
Ngoubangoye, Barthélémy ; International Centre of Medical Research of Franceville, Primatology Centre, Franceville, Gabon
Duhayer, Jeanne; Laboratoire de Biométrie et Biologie Evolutive (LBBE), UMR 5558, UCBL1, CNRS, Lyon, France
Verez, Clément; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France
Park, Chorong ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA 95616, USA ; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Dahoui, Clara; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France
Carey, Clayton M; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA ; School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA
Brennan, Greg ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA 95616, USA
Enard, David ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA
Cimarelli, Andrea ; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France
Rothenburg, Stefan ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA 95616, USA
Elde, Nels C ; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA ; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA
Pontier, Dominique ; Laboratoire de Biométrie et Biologie Evolutive (LBBE), UMR 5558, UCBL1, CNRS, Lyon, France
Etienne, Lucie ; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France
Funding: D.P. and L.E. are supported by the ANR LabEX ECOFECT [ANR-11-LABX-0048 of the Universit\u00E9 de Lyon, within the program Investissements d\u2019Avenir (ANR-11-IDEX-0007) operated by the French National Research Agency]. D.P., L.E., and S.J. are supported by the French Agence Nationale de la Recherche (ANR), under grant ANR-20-CE15-0020-01 (project \u201CBATantiVIR\u201D). L.E. and D.E. are supported by a grant from the joint program between the CNRS and the University of Arizona. L.E. is further supported by the CNRS and by grants from the French Research Agency on HIV and Emerging Infectious Diseases ANRS/MIE (nos. ECTZ19143 and ECTZ118944). D.P. is supported by the CNRS, the European Regional Development Fund (ERDF), and the ANR EBOFAC. S.J. is also supported by the Fondation L\u2019Or\u00E9al-Unesco \u201CFor Women In Science.\u201D M.E.L. is supported by NSF Rules of Life Postdoctoral Research Fellowship in Biology (NSF 2010884). S.R. was supported by grant R01 AI114851 (from the National Institute of Allergy and Infectious Diseases). N.C.E. and M.C. are supported by NIH grants R35 GM134936 and F30 GM146410 (from the National Institute of General Medical Sciences).
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