African Swine Fever (ASF) is a highly pathogenic haemorrhagic disease of swine with a severe socio-economic impact. The etiological agent is ASF virus (ASFV). Although asymptomatic in the natural host, warthog, infection of domestic pig results in extreme lethality reaching 100%. Furthermore, no vaccine is currently available. In addition to being endemic to sub-Saharan Africa and Sardinia, ASFV spread into Georgia in 2007. The virus has since expanded through the Caucasus into Russia and Eastern Europe; further dissemination is considered a threat.
ASFV is a large dsDNA virus with a 170-190kb linear genome. Terminal genome regions encode 5 clusters of paralogous genes known as multigene families (MGF). The principal variation between virulent and attenuated isolates such as the natural OURT88/3, and gene deleted isolates including BeninΔMGF is the loss of up to 6 MGF360, and 4 MGF505 genes. Infection with these viruses induces protection against challenge with virulent virus. Although the function of MGF genes has yet to be elucidated, research indicates they play a role in subverting the innate immune system. Increased IFN-β mRNA is detected in macrophages infected with viruses lacking these MGF360 and MGF505 genes compared to virulent isolates where they are present. Increased sensitivity of virus replication to pre-treatment of cells with type-I IFN is also observed. We hypothesize that these specific MGF genes interact with and block components of the interferon pathway, subduing the innate immune response to aid viral replication, thus increasing virulence. To reveal these interactions, we are using a yeast-2-hybrid system to investigate protein-protein interactions. Furthermore, observation of changes in replicative ability of ASFV possessing or lacking MGF genes in alveolar macrophages primed with IFN-α, will provide insight into the capability of resisting clearance. Understanding the functionality of the MGF proteins will aid the rational design of recombinant virus for vaccine usage.