Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases
Viruses have evolved diverse mechanisms to antagonize host immunity such as direct inhibition and relocalization of cellular APOBEC3B (A3B) by the ribonucleotide reductase (RNR) of Epstein-Barr virus. Here, we investigate the mechanistic conservation and evolutionary origin of this innate immune cou...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/83893 |
| _version_ | 1811178126898626560 |
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| author | Sofia N Moraes Jordan T Becker Seyed Arad Moghadasi Nadine M Shaban Ashley A Auerbach Adam Z Cheng Reuben S Harris |
| author_facet | Sofia N Moraes Jordan T Becker Seyed Arad Moghadasi Nadine M Shaban Ashley A Auerbach Adam Z Cheng Reuben S Harris |
| author_sort | Sofia N Moraes |
| collection | DOAJ |
| description | Viruses have evolved diverse mechanisms to antagonize host immunity such as direct inhibition and relocalization of cellular APOBEC3B (A3B) by the ribonucleotide reductase (RNR) of Epstein-Barr virus. Here, we investigate the mechanistic conservation and evolutionary origin of this innate immune counteraction strategy. First, we find that human gamma-herpesvirus RNRs engage A3B via largely distinct surfaces. Second, we show that RNR-mediated enzymatic inhibition and relocalization of A3B depend upon binding to different regions of the catalytic domain. Third, we show that the capability of viral RNRs to antagonize A3B is conserved among gamma-herpesviruses that infect humans and Old World monkeys that encode this enzyme but absent in homologous viruses that infect New World monkeys that naturally lack the A3B gene. Finally, we reconstruct the ancestral primate A3B protein and demonstrate that it is active and similarly engaged by the RNRs from viruses that infect humans and Old World monkeys but not by the RNRs from viruses that infect New World monkeys. These results combine to indicate that the birth of A3B at a critical branchpoint in primate evolution may have been a driving force in selecting for an ancestral gamma-herpesvirus with an expanded RNR functionality through counteraction of this antiviral enzyme. |
| first_indexed | 2024-04-11T06:14:03Z |
| format | Article |
| id | doaj.art-62fa70d70b3b4647b32f816eb1942dd8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T06:14:03Z |
| publishDate | 2022-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-62fa70d70b3b4647b32f816eb1942dd82022-12-22T04:41:08ZengeLife Sciences Publications LtdeLife2050-084X2022-12-011110.7554/eLife.83893Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductasesSofia N Moraes0https://orcid.org/0000-0003-0838-0047Jordan T Becker1https://orcid.org/0000-0002-0239-5443Seyed Arad Moghadasi2Nadine M Shaban3Ashley A Auerbach4https://orcid.org/0000-0001-8505-5905Adam Z Cheng5Reuben S Harris6https://orcid.org/0000-0002-9034-9112Department of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, University of Minnesota, Minneapolis, United StatesDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, University of Minnesota, Minneapolis, United StatesDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, University of Minnesota, Minneapolis, United StatesDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, University of Minnesota, Minneapolis, United StatesDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, University of Minnesota, Minneapolis, United States; Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, United StatesDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, University of Minnesota, Minneapolis, United StatesDepartment of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, University of Minnesota, Minneapolis, United States; Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, United States; Howard Hughes Medical Institute, University of Texas Health San Antonio, San Antonio, United StatesViruses have evolved diverse mechanisms to antagonize host immunity such as direct inhibition and relocalization of cellular APOBEC3B (A3B) by the ribonucleotide reductase (RNR) of Epstein-Barr virus. Here, we investigate the mechanistic conservation and evolutionary origin of this innate immune counteraction strategy. First, we find that human gamma-herpesvirus RNRs engage A3B via largely distinct surfaces. Second, we show that RNR-mediated enzymatic inhibition and relocalization of A3B depend upon binding to different regions of the catalytic domain. Third, we show that the capability of viral RNRs to antagonize A3B is conserved among gamma-herpesviruses that infect humans and Old World monkeys that encode this enzyme but absent in homologous viruses that infect New World monkeys that naturally lack the A3B gene. Finally, we reconstruct the ancestral primate A3B protein and demonstrate that it is active and similarly engaged by the RNRs from viruses that infect humans and Old World monkeys but not by the RNRs from viruses that infect New World monkeys. These results combine to indicate that the birth of A3B at a critical branchpoint in primate evolution may have been a driving force in selecting for an ancestral gamma-herpesvirus with an expanded RNR functionality through counteraction of this antiviral enzyme.https://elifesciences.org/articles/83893APOBEC3Bevolutionary arms raceherpesvirushost-pathogen interactionribonucleotide reductaseviral evolution |
| spellingShingle | Sofia N Moraes Jordan T Becker Seyed Arad Moghadasi Nadine M Shaban Ashley A Auerbach Adam Z Cheng Reuben S Harris Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases eLife APOBEC3B evolutionary arms race herpesvirus host-pathogen interaction ribonucleotide reductase viral evolution |
| title | Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases |
| title_full | Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases |
| title_fullStr | Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases |
| title_full_unstemmed | Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases |
| title_short | Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases |
| title_sort | evidence linking apobec3b genesis and evolution of innate immune antagonism by gamma herpesvirus ribonucleotide reductases |
| topic | APOBEC3B evolutionary arms race herpesvirus host-pathogen interaction ribonucleotide reductase viral evolution |
| url | https://elifesciences.org/articles/83893 |
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