Peste des petits ruminants virus (PPRV) is a morbillivirus that produces clinical disease in goats and sheep. We have studied the induction of interferon-β (IFN-β) following infection of cultured cells with wild-type and vaccine strains of PPRV, and the effects of such infection with PPRV on the induction of IFN-β through both MDA-5 and RIG-I mediated pathways. Using both reporter assays and direct measurement of IFN-β mRNA, we have found that PPRV infection induces IFN-β only weakly and transiently, and the virus can actively block the induction of IFN-β. We have also generated mutant PPRV that lack expression of either of the viral accessory proteins (V&C) to characterize the role of these proteins in IFN-β induction during virus infection. Both PPRV_ΔV and PPRV_ΔC were defective in growth in cell culture, although in different ways. While the PPRV V protein bound to MDA-5 and, to a lesser extent, RIG-I, and over-expression of the V protein inhibited both IFN-β induction pathways, PPRV lacking V protein expression can still block IFN-β induction. In contrast, PPRV C bound to neither MDA-5 nor RIG-I, but PPRV lacking C protein expression lost the ability to block both MDA-5 and RIG-I mediated activation of IFN-β. These results shed new light on the inhibition of the induction of IFN-β by PPRV.
The V proteins of paramyxoviruses are composed of two evolutionarily distinct domains, the N-terminal 75 % being common to the viral P, V and W proteins, and not highly conserved between viruses, whilst the remaining 25 % consists of a cysteine-rich V-specific domain, which is conserved across almost all paramyxoviruses. There is evidence supporting a number of different functions of the V proteins of morbilliviruses in blocking the signalling pathways of type I and II IFNs, but it is not clear which domains of V are responsible for which activities and whether all these activities are required for effective blockade of IFN signalling. We have shown here that the two domains of rinderpest virus V protein have distinct functions: the N-terminal domain acted to bind STAT1, whilst the C-terminal V-specific domain interacted with the IFN receptor-associated kinases Jak1 and Tyk2. Effective blockade of IFN signalling required the intact V protein.
Lumpy skin disease (LSD) is a tropical neglected viral disease of cattle, characterised by numerous cutaneous lesions disseminated throughout the body. Historically endemic to the African continent, it has become a threat to Europe following the outbreaks of LSD in the Middle East and Eastern Europe. LSD virus (LSDV) is a Capripoxvirus transmitted by insect vectors. Experimental and epidemiological studies have indicated a role for the stable fly (Stomoxys calcintrans) and the mosquito Aedes aegypti. Nevertheless the relative importance of these vector species and others is unclear. A study was designed to explore the risk of transmission of LSDV from cattle to different vector species including Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus. Cattle was challenged with LSDV to produce a bovine experimental model used as a natural source of LSDV to the potential vectors. Cattle samples were taken to quantify LSDV in different tissues and characterise the disease. All insect species were allowed to feed on LSDV-challenged cattle at regular intervals and incubated for up to eight days. This data was then used to model the dynamics of LSDV infection and transmission. All four species were able to acquire and maintain LSDV for up to eight days post feeding, and the risk of transmission from bovine donor to insect was dependent on the severity of the disease. A model was then generated using ex-vivo skin lesions and infectious blood that will allow further studies of the role of these vectors.
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