Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct 3;8(4):585.
doi: 10.3390/vaccines8040585.

Role of the DNA-Binding Protein pA104R in ASFV Genome Packaging and as a Novel Target for Vaccine and Drug Development

Ana Catarina Urbano  1 , Fernando Ferreira  1
Affiliations
Review

Role of the DNA-Binding Protein pA104R in ASFV Genome Packaging and as a Novel Target for Vaccine and Drug Development

Ana Catarina Urbano et al. Vaccines (Basel). .

Abstract

The recent incursions of African swine fever (ASF), a severe, highly contagious, transboundary viral disease that affects members of the Suidae family, in Europe and China have had a catastrophic impact on trade and pig production, with serious implications for global food security. Despite efforts made over past decades, there is no vaccine or treatment available for preventing and controlling the ASF virus (ASFV) infection, and there is an urgent need to develop novel strategies. Genome condensation and packaging are essential processes in the life cycle of viruses. The involvement of viral DNA-binding proteins in the regulation of virulence genes, transcription, DNA replication, and repair make them significant targets. pA104R is a highly conserved HU/IHF-like DNA-packaging protein identified in the ASFV nucleoid that appears to be profoundly involved in the spatial organization and packaging of the ASFV genome. Here, we briefly review the components of the ASFV packaging machinery, the structure, function, and phylogeny of pA104R, and its potential as a target for vaccine and drug development.

Keywords: ASFV; African swine fever; NCLDV; antiviral therapy; genome packaging; pA104R; stilbenes; vaccine; viral DNA-packaging proteins.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The structure of pA104R: (a) Model of dimeric pA104R generated by the Schrödinger Maestro suite [59]; (b) One protomer of the dimeric pA104R; (c) Topological diagram of secondary structural elements of the pA104R protomer; (d) Model of pA104R (magenta) superimposed with M. tuberculosis HU (cyan). The lengthened beta 2–3 and 4–5 loops are encircled; (e) Multiple sequence alignment of pA104R with other HU/IHF members generated by Clustal Omega (version 1.2.4) [60] using the HHalign algorithm and its default settings as described in [61] and ESPript 3.x [62]. The extra two sets of amino acids are highlighted in yellow; (f) The positively charged amino acid residues in the bottom (K92, R94, and K97) and arm regions (R69, H72, K83, and K85) of the pA104R protomer that contribute the majority of the protein-DNA interactions. The PDB codes of the structures are 6LMH (pA104R) and 4PT4 (mtbHU). Accession numbers are P68742, P0A6X7, P0A6Y1, B1YQ53, A0A2A7DF13, Q99U17, and P9WMK7.
Figure 2
Figure 2
Phylogenetic analysis of pA104R: (a) Phylogenetic tree of DNABII bacterial sequences. Blue labels represent Proteobacteria sequences. Red labels represent Terrabacteria group sequences. Grey labels represent other bacterial sequences; (b) Phylogenetic tree of DNABII viral sequences. Blue labels represent sequences whose host species belong to the Proteobacteria phylum. Red labels represent sequences whose host species belong to the Terrabacteria group; (c) Phylogenetic tree of DNABII eukaryotic sequences. Blue labels represent organisms of the phylum Apicomplexa. Sus scrofa and Ornithodoros moubata histones H2B were chosen as an outgroup (red). A BLAST (version 2.10.0) search of the nonredundant protein database was performed using BLOSUM62 matrix and default settings (Expectation value 10, Low complexity filtering, Max No. of answers 25, Word size 3). Sequences having scores >45, E value <0.1, and >25% identity were selected. Trees were generated by MEGA X (version 10.1.8) [75] using the Maximum Likelihood method and Tamura-Nei model [76] and iTOL (version 4) [77] from a multiple sequence alignment of the relevant sequences generated by MAFFT (version 7) online service using the default settings as described in [78]. The reliability of the tree topology was assessed using Felsenstein’s bootstrap test [79], with 1000 replications. Bootstrap values are shown next to the branches. The scale bars indicate the expected number of amino acid substitutions per site. Accession numbers are indicated in the labels.
Figure 3
Figure 3
Phylogenetic tree of 64 different ASFV isolates. Geographic distribution and p72 genotype of ASFV isolates are indicated. Nucleotide sequences were obtained from NCBI nucleotide collection database. Trees were generated by MEGA X (version 10.1.8) [75] using the Maximum Likelihood method and Tamura-Nei model [76] and iTOL (version 4) [77] from a multiple sequence alignment generated by MAFFT (version 7) online service using the default settings as described in [78]. The reliability of the tree topology was assessed using Felsenstein’s bootstrap test [79], with 1000 replications. Bootstrap values are shown next to the branches. The scale bars indicate the expected number of amino acid substitutions per site. Accession numbers are indicated in the labels.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Costard S., Mur L., Lubroth J., Sanchez-Vizcaino J.M., Pfeiffer D.U. Epidemiology of African swine fever virus. Virus Res. 2013;173:191–197. doi: 10.1016/j.virusres.2012.10.030. - DOI - PubMed
    1. Alonso C., Borca M., Dixon L., Revilla Y., Rodriguez F., Escribano J.M. ICTV virus taxonomy profile: Asfarviridae. J. Gen. Virol. 2018;99:613–614. doi: 10.1099/jgv.0.001049. - DOI - PubMed
    1. World Organisation for Animal Health . African Swine Fever (ASF) WAHIS; Paris, France: 2020. Global Situation of African Swine Fever. Report N°47: 2016–2020.
    1. World Organisation for Animal Health . African Swine Fever (ASF) WAHIS; Paris, France: 2020. ASF Situation. Report N°52: 21 August–3 September 2020.
    1. Chapman D.A.G., Darby A.C., Da Silva M., Upton C., Radford A.D., Dixon L.K. Genomic analysis of highly virulent Georgia 2007/1 isolate of African swine fever virus. Emerg. Infect. Dis. 2011;17:599–605. doi: 10.3201/eid1704.101283. - DOI - PMC - PubMed

LinkOut - more resources