African swine fever virus (ASFV) poses one of the greatest threats to pig farming worldwide. It is
highly infectious and causes rapid haemorrhagic death of domestic pigs and Eurasian wild boar (Sus
scrofa). In contrast, native African pig species (bushpigs and warthogs) suffer only a mild,
subclinical form of the infection from which they rapidly recover. It is hypothesised that the striking
difference in the pathophysiological consequences of ASFV infection may reflect a variable ability
of the virus to modulate the host immune response in these species. Alternatively, it may indicate a
fundamental evolutionary distinction between the immune responses of these animals.
In common with many other DNA viruses, ASFV has evolved a complex strategy for modulating the
host-cell immune response. The ASFV-encoded protein, A238L, targets key sites within both the
NFkB and NFAT immune-signalling pathways. Furthermore, the ASFV protein, p54, is involved in
attachment of virus particles to the microtubule motor complex, cytoplasmic dynein. This may
represent a key stage in the infection process. Six host proteins targeted or mimicked by A238L and
p54 (light chain dynein, cyclophilin A, calcineurin A, NFAT, p65 (RelA) and IkΒα) have been
sequenced in the susceptible domestic pig, resistant warthog and phenotypically unknown babirusa.
In addition, the ~1.6kbp promoter driving expression of the proinflammatory cytokine, tumour
necrosis factor alpha (TNFα), has also been studied.
Despite identifying high levels of nucleotide sequence conservation in these genes, polymorphisms
have been identified in the NFkB subunit p65 (RelA) and the TNFα promoter. These may be of
functional significance in determining the immune response characteristic of the different pig
species studied. These polymorphisms have been further explored using in vitro expression and
luciferase-reporter analysis. Furthermore, the identification of these sites has enabled the
commercial sponsor of this project, Sygen International, to screen their domestic pig lines for
'warthog-like' sequence, which may confer some degree of disease resistance.
These findings provide a valuable insight into potential mechanisms involved in altered host
susceptibility to African swine fever. In addition, this study may have wider-reaching implications
for understanding issues of both susceptibility and pathogenesis relating to other infectious diseases
of both humans and animals.