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Volume 14
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10.3390/v14112348
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Article

In Silico Characterization of African Swine Fever Virus Nucleoprotein p10 Interaction with DNA

by
Claudia Istrate
1,2,
Jéssica Marques
3,
Pedro Bule
1,2,
Sílvia Correia
1,2,
Frederico Aires-da-Silva
1,2,
Marlene Duarte
1,2,
Ana Luísa Reis
4,
Miguel Machuqueiro
3,
Alexandre Leitão
1,2,* and
Bruno L. Victor
3,*
1
CIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisboa, Portugal
2
Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal
3
BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisboa, Portugal
4
The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, UK
*
Authors to whom correspondence should be addressed.
Viruses 2022, 14(11), 2348; https://doi.org/10.3390/v14112348
Submission received: 17 September 2022 / Revised: 21 October 2022 / Accepted: 22 October 2022 / Published: 25 October 2022
(This article belongs to the Special Issue African Swine Fever Virus 2.0)
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Abstract

African swine fever virus (ASFV) is the etiological agent of a highly contagious, hemorrhagic infectious swine disease, with a tremendous sanitary and economic impact on a global scale. Currently, there are no globally available vaccines or treatments. The p10 protein, a structural nucleoprotein encoded by ASFV, has been previously described as capable of binding double-stranded DNA (dsDNA), which may have implications for viral replication. However, the molecular mechanism that governs this interaction is still unknown, mostly due to the lack of a structural model for this protein. In this work, we have generated an ab initio model of the p10 protein and performed extensive structural characterization, using molecular dynamics simulations to identify the motifs and residues regulating DNA recognition. The helix-turn-helix motif identified at the C-terminal region of the protein was shown to be crucial to the dsDNA-binding efficiency. As with other DNA-binding proteins, two distinct serine and lysine-rich regions found in the two helices were identified as key players in the binding to DNA, whose importance was later validated using experimental binding assays. Altogether, these findings may contribute to a better understanding of the p10 function in ASFV replication.
Keywords: African swine fever virus; p10 protein; molecular dynamics; DNA binding function; K78R African swine fever virus; p10 protein; molecular dynamics; DNA binding function; K78R

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MDPI and ACS Style

Istrate, C.; Marques, J.; Bule, P.; Correia, S.; Aires-da-Silva, F.; Duarte, M.; Reis, A.L.; Machuqueiro, M.; Leitão, A.; Victor, B.L. In Silico Characterization of African Swine Fever Virus Nucleoprotein p10 Interaction with DNA. Viruses 2022, 14, 2348. https://doi.org/10.3390/v14112348

AMA Style

Istrate C, Marques J, Bule P, Correia S, Aires-da-Silva F, Duarte M, Reis AL, Machuqueiro M, Leitão A, Victor BL. In Silico Characterization of African Swine Fever Virus Nucleoprotein p10 Interaction with DNA. Viruses. 2022; 14(11):2348. https://doi.org/10.3390/v14112348

Chicago/Turabian Style

Istrate, Claudia, Jéssica Marques, Pedro Bule, Sílvia Correia, Frederico Aires-da-Silva, Marlene Duarte, Ana Luísa Reis, Miguel Machuqueiro, Alexandre Leitão, and Bruno L. Victor. 2022. "In Silico Characterization of African Swine Fever Virus Nucleoprotein p10 Interaction with DNA" Viruses 14, no. 11: 2348. https://doi.org/10.3390/v14112348

APA Style

Istrate, C., Marques, J., Bule, P., Correia, S., Aires-da-Silva, F., Duarte, M., Reis, A. L., Machuqueiro, M., Leitão, A., & Victor, B. L. (2022). In Silico Characterization of African Swine Fever Virus Nucleoprotein p10 Interaction with DNA. Viruses, 14(11), 2348. https://doi.org/10.3390/v14112348

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