Coevolution of Lentiviral Vif with Host A3F and A3G: Insights from Computational Modelling and Ancestral Sequence Reconstruction
The evolutionary arms race between host restriction factors and viral antagonists provides crucial insights into immune system evolution and viral adaptation. This study investigates the structural and evolutionary dynamics of the double-domain restriction factors A3F and A3G and their viral inhibit...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/1999-4915/17/3/393 |
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| author | David Nicolas Giuseppe Huebert Atefeh Ghorbani Shaw Yick Brian Lam Mani Larijani |
| author_facet | David Nicolas Giuseppe Huebert Atefeh Ghorbani Shaw Yick Brian Lam Mani Larijani |
| author_sort | David Nicolas Giuseppe Huebert |
| collection | DOAJ |
| description | The evolutionary arms race between host restriction factors and viral antagonists provides crucial insights into immune system evolution and viral adaptation. This study investigates the structural and evolutionary dynamics of the double-domain restriction factors A3F and A3G and their viral inhibitor, Vif, across diverse primate species. By constructing 3D structural homology models and integrating ancestral sequence reconstruction (ASR), we identified patterns of sequence diversity, structural conservation, and functional adaptation. Inactive CD1 (Catalytic Domain 1) domains displayed greater sequence diversity and more positive surface charges than active CD2 domains, aiding nucleotide chain binding and intersegmental transfer. Despite variability, the CD2 DNA-binding grooves remained structurally consistent with conserved residues maintaining critical functions. A3F and A3G diverged in loop 7’ interaction strategies, utilising distinct molecular interactions to facilitate their roles. Vif exhibited charge variation linked to host species, reflecting its coevolution with A3 proteins. These findings illuminate how structural adaptations and charge dynamics enable both restriction factors and their viral antagonists to adapt to selective pressures. Our results emphasize the importance of studying structural evolution in host–virus interactions, with implications for understanding immune defense mechanisms, zoonotic risks, and viral evolution. This work establishes a foundation for further exploration of restriction factor diversity and coevolution across species. |
| format | Article |
| id | doaj-art-af090dbbe4a24e0dbb9e916ed09e2867 |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj-art-af090dbbe4a24e0dbb9e916ed09e28672025-08-20T02:43:10ZengMDPI AGViruses1999-49152025-03-0117339310.3390/v17030393Coevolution of Lentiviral Vif with Host A3F and A3G: Insights from Computational Modelling and Ancestral Sequence ReconstructionDavid Nicolas Giuseppe Huebert0Atefeh Ghorbani1Shaw Yick Brian Lam2Mani Larijani3Immunology and Infectious Diseases Program, Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1C 5S7, CanadaImmunology and Infectious Diseases Program, Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1C 5S7, CanadaStructural Biology and Immunology Program, Department of Molecular Biology and Biochemistry, Faculty of Science, Simon Fraser University, Burnaby, BC V5A 1S6, CanadaImmunology and Infectious Diseases Program, Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1C 5S7, CanadaThe evolutionary arms race between host restriction factors and viral antagonists provides crucial insights into immune system evolution and viral adaptation. This study investigates the structural and evolutionary dynamics of the double-domain restriction factors A3F and A3G and their viral inhibitor, Vif, across diverse primate species. By constructing 3D structural homology models and integrating ancestral sequence reconstruction (ASR), we identified patterns of sequence diversity, structural conservation, and functional adaptation. Inactive CD1 (Catalytic Domain 1) domains displayed greater sequence diversity and more positive surface charges than active CD2 domains, aiding nucleotide chain binding and intersegmental transfer. Despite variability, the CD2 DNA-binding grooves remained structurally consistent with conserved residues maintaining critical functions. A3F and A3G diverged in loop 7’ interaction strategies, utilising distinct molecular interactions to facilitate their roles. Vif exhibited charge variation linked to host species, reflecting its coevolution with A3 proteins. These findings illuminate how structural adaptations and charge dynamics enable both restriction factors and their viral antagonists to adapt to selective pressures. Our results emphasize the importance of studying structural evolution in host–virus interactions, with implications for understanding immune defense mechanisms, zoonotic risks, and viral evolution. This work establishes a foundation for further exploration of restriction factor diversity and coevolution across species.https://www.mdpi.com/1999-4915/17/3/393Apobec3Viflentiviruseshost–viral coevolutionviral antagonistsdeamination |
| spellingShingle | David Nicolas Giuseppe Huebert Atefeh Ghorbani Shaw Yick Brian Lam Mani Larijani Coevolution of Lentiviral Vif with Host A3F and A3G: Insights from Computational Modelling and Ancestral Sequence Reconstruction Viruses Apobec3 Vif lentiviruses host–viral coevolution viral antagonists deamination |
| title | Coevolution of Lentiviral Vif with Host A3F and A3G: Insights from Computational Modelling and Ancestral Sequence Reconstruction |
| title_full | Coevolution of Lentiviral Vif with Host A3F and A3G: Insights from Computational Modelling and Ancestral Sequence Reconstruction |
| title_fullStr | Coevolution of Lentiviral Vif with Host A3F and A3G: Insights from Computational Modelling and Ancestral Sequence Reconstruction |
| title_full_unstemmed | Coevolution of Lentiviral Vif with Host A3F and A3G: Insights from Computational Modelling and Ancestral Sequence Reconstruction |
| title_short | Coevolution of Lentiviral Vif with Host A3F and A3G: Insights from Computational Modelling and Ancestral Sequence Reconstruction |
| title_sort | coevolution of lentiviral vif with host a3f and a3g insights from computational modelling and ancestral sequence reconstruction |
| topic | Apobec3 Vif lentiviruses host–viral coevolution viral antagonists deamination |
| url | https://www.mdpi.com/1999-4915/17/3/393 |
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