African Swine Fever immune evasion strategies

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African swine fever virus (ASFV) can result in very high mortality in domestic pigs, although persistent asymptomatic infections are observed in natural hosts including warthogs, bushpigs and soft ticks. Some less virulent isolates have been described, which either result in reduced mortality or cause few disease signs. The genome contains between 160 and 175 open reading frames, including many encoding proteins involved in evading host defence systems. The aims are to identify the molecular basis of virus pathogenesis and immune modulation. A practical outcome will be the development of effective vaccines. One approach involves studying the function of virus-encoded proteins involved in immune evasion, by identifying target proteins they interact with, their localisation within cells and host pathways they modulate. The methods used involve construction of ASFV gene deletion mutants and comparison of infections with wild type and mutant ASFV as well as studies using the expressed proteins. Virus proteins currently studied include a transmembrane protein, CD2v, which resembles the host CD2 protein in its extracellular domain. CD2v is known to be required for inhibition of lymphocyte proliferation and the mechanism by which it does this is under investigation as well as other functions of the protein. Studies of a virus inhibitor of toll-like receptor signalling have been initiated (in collaboration with Mike Parkhouse IGC, Oeiras) and studies on other novel immune evasion proteins will follow. A second approach involves comparison of complete genome sequences from high and low virulence isolates to identify genomic differences and comparing host responses following infections of macrophages, the main target cell for ASFV replication in vitro. Changes in host transcription that occur following infection with low and high virulence isolates have been characterised using microarrays and quantitative reverse transcriptase PCR.

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