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Review
. 2020 Aug 28;48(4):1569-1581.
doi: 10.1042/BST20191108.

Transcriptome view of a killer: African swine fever virus

Gwenny Cackett  1 , Michal Sýkora  1 , Finn Werner  1
Affiliations
Review

Transcriptome view of a killer: African swine fever virus

Gwenny Cackett et al. Biochem Soc Trans. .

Abstract

African swine fever virus (ASFV) represents a severe threat to global agriculture with the world's domestic pig population reduced by a quarter following recent outbreaks in Europe and Asia. Like other nucleocytoplasmic large DNA viruses, ASFV encodes a transcription apparatus including a eukaryote-like RNA polymerase along with a combination of virus-specific, and host-related transcription factors homologous to the TATA-binding protein (TBP) and TFIIB. Despite its high impact, the molecular basis and temporal regulation of ASFV transcription is not well understood. Our lab recently applied deep sequencing approaches to characterise the viral transcriptome and gene expression during early and late ASFV infection. We have characterised the viral promoter elements and termination signatures, by mapping the RNA-5' and RNA-3' termini at single nucleotide resolution. In this review, we discuss the emerging field of ASFV transcripts, transcription, and transcriptomics.

Keywords: African swine fever virus; RNA polymerase; RNA sequencing; gene expression and regulation; transcription; virology.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1.
Figure 1.. RNA polymerases from ASFV is closely related to eukaryotic Pol II.
(a) Diagrammatic representation of eukaryotic Pol II from S. cerevisiae drawn from PDB: 6GYK. CTD refers to the ‘carboxy terminal domain’. (b) The NCLDV-RNAP represented by ASFV-RNAP. This diagrammatic model was drawn from PHYRE2 homology models [114] for ASFV homologs of Pol II subunits, mapped onto the Pol II structure using UCSF Chimera [115]. Homologous RNAP subunits are colour-coded and annotated, please note that the RPB3 and 11 subunits are fused in both ASFV and VACV, and ASFV-RPB7 contains an extended C-terminus, with no homology to characterised proteins [24,28]. Additionally, beyond canonical Pol II subunits, NCLDV-RNAPs also include, based on structurally characterised VACV-RNAP, a stably integrated mRNA capping enzyme (NP868R, highlighted in pale green) and termination factor (Q706L, in pale red) [28,29].
Figure 2.
Figure 2.. Temporal ASFV gene expression.
(a) Differentially expressed genes during early and late infection of Vero cells with ASFV strain BA71V are categorised according to function: early (down-regulated) and late (up-regulated) genes are indicated in blue and red, respectively. (b) Venn diagram of highest 17 expressed ASFV genes detected in the blood of GRG-infected pigs using RNA-seq by Jaing et al. [64]. The two lower sectors correspond to 20 genes most expressed during early (5 h, left) and late (16 h, right) infection of Vero cells, regardless of differential expression, characterised by CAGE-seq [58]. Genes are colour-coded according to their predicted functional group (as in (a)): the group ‘information processing’ is a combination of ‘Transcription/RNA modification’, NA metabolism/DNA replication & repair’ and Genome organisation’.
Figure 3.
Figure 3.. DNA consensus motifs for ASFV promoters, initiators and terminators.
The sequence features of early and late gene promoter regions, including the EPM (a), LPM (b) and Inr elements (c and d). Note that spacing between the promoter motif and Inr varies in early and late gene promoters. Transcription termination is associated with a polyT signature (e and f), though a significant number of ASFV genes do not contain this termination motif hinting at an alternative, possibly factor-dependent, mode of termination.
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