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Structural basis for hijacking of the host ACBD3 protein by bovine and porcine enteroviruses and kobuviruses

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Abstract

Picornaviruses infect a wide range of mammals including livestock such as cattle and swine. As with other picornavirus genera such as Aphthovirus, there is emerging evidence of a significant economic impact of livestock infections caused by members of the genera Enterovirus and Kobuvirus. While the human-infecting enteroviruses and kobuviruses have been intensively studied during the past decades in great detail, research on livestock-infecting viruses has been mostly limited to the genomic characterization of the viral strains identified worldwide. Here, we extend our previous studies of the structure and function of the complexes composed of the non-structural 3A proteins of human-infecting enteroviruses and kobuviruses and the host ACBD3 protein and present a structural and functional characterization of the complexes of the following livestock-infecting picornaviruses: bovine enteroviruses EV-E and EV-F, porcine enterovirus EV-G, and porcine kobuvirus AiV-C. We present a series of crystal structures of these complexes and demonstrate the role of these complexes in facilitation of viral replication.

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Acknowledgements

We are grateful to Carolyn Machamer for sharing the ACBD3-encoding plasmid, and Frank JM van Kuppeveld for fruitful discussions. We thank Helmholtz-Zentrum Berlin for the allocation of synchrotron radiation beamtime. The project was supported by the Czech Science Foundation (Grant number 17-07058Y), Czech Academy of Sciences (RVO: 61388963), and European Regional Development Fund (ERDF/ESF project “Chemical biology for drugging undruggable targets-ChemBioDrug”, number CZ.02.1.01/0.0/0.0/16_019/0000729).

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Author notes

  1. Miroslav Smola and Vladimira Horova contributed equally.

Authors and Affiliations

  1. Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic

    Miroslav Smola, Vladimira Horova, Evzen Boura & Martin Klima

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  1. Miroslav Smola
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  2. Vladimira Horova
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  3. Evzen Boura
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Contributions

MS performed DNA cloning, protein purifications, and crystallographic experiments, VH contributed to DNA cloning, carried out microscale thermophoresis, the co-immunoprecipitation and viral subgenomic replicon assays, EB conceived the study and revised the manuscript, MK supervised the project, solved the crystal structures, and wrote the manuscript.

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Correspondence to Evzen Boura or Martin Klima.

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Handling Editor: Diego G. Diel.

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Smola, M., Horova, V., Boura, E. et al. Structural basis for hijacking of the host ACBD3 protein by bovine and porcine enteroviruses and kobuviruses. Arch Virol 165, 355–366 (2020). https://doi.org/10.1007/s00705-019-04490-9

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