Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions

Stéphanie Jacquet; Michelle Culbertson; Chi Zhang; Adil El Filali; Clément De La Myre Mory; Jean Baptiste Pons; Ondine Filippi-Codaccioni; M. Elise Lauterbur; Barthélémy Ngoubangoye; Jeanne Duhayer; Clément Verez; Chorong Park; Clara Dahoui; Clayton M. Carey; Greg Brennan; David Enard; Andrea Cimarelli; Stefan Rothenburg; Nels C. Elde; Dominique Pontier; Lucie Etienne

doi:10.1126/sciadv.add7540

Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions

Stéphanie Jacquet, Michelle Culbertson, Chi Zhang, Adil El Filali, Clément De La Myre Mory, Jean Baptiste Pons, Ondine Filippi-Codaccioni, M. Elise Lauterbur, Barthélémy Ngoubangoye, Jeanne Duhayer, Clément Verez, Chorong Park, Clara Dahoui, Clayton M. Carey, Greg Brennan, David Enard, Andrea Cimarelli, Stefan Rothenburg, Nels C. Elde, Dominique PontierLucie Etienne

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Abstract

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.

Original language	English (US)
Article number	eadd7540
Journal	Science Advances
Volume	8
Issue number	47
DOIs	https://doi.org/10.1126/sciadv.add7540
State	Published - Nov 25 2022

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Jacquet, S., Culbertson, M., Zhang, C., El Filali, A., De La Myre Mory, C., Pons, J. B., Filippi-Codaccioni, O., Lauterbur, M. E., Ngoubangoye, B., Duhayer, J., Verez, C., Park, C., Dahoui, C., Carey, C. M., Brennan, G., Enard, D., Cimarelli, A., Rothenburg, S., Elde, N. C., ... Etienne, L. (2022). Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions. Science Advances, 8(47), Article eadd7540. https://doi.org/10.1126/sciadv.add7540

Jacquet, S, Culbertson, M, Zhang, C, El Filali, A, De La Myre Mory, C, Pons, JB, Filippi-Codaccioni, O, Lauterbur, ME, Ngoubangoye, B, Duhayer, J, Verez, C, Park, C, Dahoui, C, Carey, CM, Brennan, G, Enard, D, Cimarelli, A, Rothenburg, S, Elde, NC, Pontier, D & Etienne, L 2022, 'Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions', Science Advances, vol. 8, no. 47, eadd7540. https://doi.org/10.1126/sciadv.add7540

@article{863599d270b84c6ca4de46188ae7caaf,

title = "Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions",

abstract = "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.",

author = "St{\'e}phanie Jacquet and Michelle Culbertson and Chi Zhang and {El Filali}, Adil and {De La Myre Mory}, Cl{\'e}ment and Pons, {Jean Baptiste} and Ondine Filippi-Codaccioni and Lauterbur, {M. Elise} and Barth{\'e}l{\'e}my Ngoubangoye and Jeanne Duhayer and Cl{\'e}ment Verez and Chorong Park and Clara Dahoui and Carey, {Clayton M.} and Greg Brennan and David Enard and Andrea Cimarelli and Stefan Rothenburg and Elde, {Nels C.} and Dominique Pontier and Lucie Etienne",

note = "Funding Information: Funding: D.P. and L.E. are supported by the ANR LabEX ECOFECT [ANR-11-LABX-0048 of the Universit{\'e} de Lyon, within the program Investissements d{\textquoteright}Avenir (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 “BATantiVIR”). 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{\textquoteright}Or{\'e}al-Unesco “For Women In Science.” 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). Publisher Copyright: 2022 The Authors, some rights reserved;",

year = "2022",

month = nov,

day = "25",

doi = "10.1126/sciadv.add7540",

language = "English (US)",

volume = "8",

journal = "Science Advances",

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TY - JOUR

T1 - Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions

AU - Jacquet, Stéphanie

AU - Culbertson, Michelle

AU - Zhang, Chi

AU - El Filali, Adil

AU - De La Myre Mory, Clément

AU - Pons, Jean Baptiste

AU - Filippi-Codaccioni, Ondine

AU - Lauterbur, M. Elise

AU - Ngoubangoye, Barthélémy

AU - Duhayer, Jeanne

AU - Verez, Clément

AU - Park, Chorong

AU - Dahoui, Clara

AU - Carey, Clayton M.

AU - Brennan, Greg

AU - Enard, David

AU - Cimarelli, Andrea

AU - Rothenburg, Stefan

AU - Elde, Nels C.

AU - Pontier, Dominique

AU - Etienne, Lucie

N1 - Funding Information: Funding: D.P. and L.E. are supported by the ANR LabEX ECOFECT [ANR-11-LABX-0048 of the Université de Lyon, within the program Investissements d’Avenir (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 “BATantiVIR”). 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’Oréal-Unesco “For Women In Science.” 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). Publisher Copyright: 2022 The Authors, some rights reserved;

PY - 2022/11/25

Y1 - 2022/11/25

N2 - 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.

AB - 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.

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Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions

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