Phylogenetic Analysis of the Histone-like Protein (pA104R) Reveals High Conservation among African Swine Fever Virus (ASFV) Variants

Abstract

The African Swine Fever Virus (ASFV) is a highly lethal virus that causes the death of pigs a week after its symptoms begin to manifest; hence, a mortality rate reaching up to 100%. Because of the crucial role of pork as a food preference worldwide, significant economic losses due to ASF outbreaks have been experienced. Despite the severity of this disease, there is still no known treatment that can successfully cure ASF. Recently, the role of the histone-like protein pA104R in the viral replication of ASFV has been unraveled and is gathering the attention of many researchers as a potential target to inhibit ASFV infectivity. However, little is known about the relationship of this protein with its homologs across variants of ASF. Therefore, in this study, we characterized their relationship and highlight conserved and variable regions that allow for the design of effective inhibitors. We acquired the nucleotide sequences of all pA104R homologs through the tBLASTn program. These sequences were subjected to multiple sequence alignment (MSA), and the evolutionary behavior of the sequences was then mapped out. The resulting tree was produced from 91 sequences taken from the NCBI database and contained five distinct clades. The phylogenetic analysis revealed that variants from clades “C” and “E” were highly variable, reflecting higher frequencies of gene mutation compared to the other clades. The alignment and midpoint-rooted phylogenetic tree showed the high conservation of pA104R across variants of ASFV. The variable residues were also determined. From these results, we conclude that drugs and drug-like compounds that can block the protein-DNA binding sites can be administered to afflicted pigs all over the world due to the high conservation of the protein across virulent strains. Thus, pA104R has high potential as a target protein for the inhibition of ASFV replication and spread.