BBSRC-funded studentship: Role of Interferon-regulated genes in the control of African swine fever virus replication

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

African swine fever virus (ASFV), which is a large double-stranded DNA virus, is the causative agent of a lethal haemorrhagic disease of the domestic pig. There is no vaccine available and disease control relies on movement restriction and slaughter. ASFV is a threat to UK farmers as well as being devastating to subsistence farmers and the rural poor in Africa. In Africa, the virus exists in a sylvatic cycle between soft ticks (family Ornithodoros) and the native suids, the warthog and the bushpig. The virus is essentially asymptomatic in these natural hosts, which can remain persistently infected over several years, and only causes disease in the domestic pig and wild boar. There is increasing evidence that the host interferon (IFN) response is important in determining the outcome of infection with ASFV. Treatment of virus susceptible cells with IFN leads to a significant reduction in virus titres. Preliminary data suggests that ASFV isolates may differ in their ability to replicate in the presence of porcine IFN-gamma and this difference may be linked to virulence. Although IFN-inducible porcine genes required to limit ASFV replication have not been defined, we have recently demonstrated that a human IFN-regulated gene, MxA, can effectively inhibit ASFV eplication in vitro. Mx is known to have antiviral activity against a wide range of RNA viruses, and this is the first description of Mx inhibiting a large double-stranded DNA virus. Preliminary studies suggest that porcine Mx1, the porcine homolog of MxA, may act in a similar way to MxA. We hypothesise that IFN-regulated genes are required to limit ASFV replication and that virus virulence is linked to the ability of the virus to overcome the anti-viral state. The aims of this project are, therefore, to determine the role of IFN-regulated genes in the pathogenesis of ASFV and to identify the porcine IFN-regulated genes that are required to inhibit ASFV replication.

Publications

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