African swine fever virus genes involved in modifying virulence and host responses

African swine fever virus (ASFV) is a large cytoplasmic double-stranded DNA virus, which encodes many proteins that are not essential for ASFV replication in cells, but have important roles in virus survival and transmission in its hosts, including those which help it evade the host’s innate and adaptive immune responses. ASFV causes a haemorrhagic fever in domestic pigs and can result in very high mortality leadimg to severe socio-economic impact. There is no vaccine and this limits options for disease control. A better understanding of how ASFV manipulates the host response to infection will underpin the development of effective vaccines. In this project we will continue to identify and investigate the function of ASFV proteins involved in virulence and in modulating host responses to infection. Key proteins, such as the protein phosphatase 1 regulator DP71L, already known to have roles in these processes will be further investigated. We have already shown DP71L inhibits stress-induced shut-off of global protein synthesis and we will investigate the hypothesis that DP71L has additional roles mediated through targeting PP1 to specific substrates. The ASFV transmembrane protein, CD2v, is required to facilitate virus dissemination in pigs and to impair the ability of lymphocytes to proliferate. The presence of the CD2v gene also enhances virus replication in the tick vector Ornithodoros at the level of virus uptake in the tick gut. We will identify cellular ligands for CD2v and define key functional domains. Novel proteins involved in modulating host responses and other functions will be identified using an ASFV expression library. The effect of deleting these and other genes from the ASFV genome will be investigated. Virus replication and host responses will be studied in macrophage cultures and in immunisation and challenge experiments in pigs to establish candidate attenuated vaccine strains.