Abstract

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.

Highlights

  • Peste des petits ruminants (PPR) is a viral disease of sheep, goats and related wild animals. It is caused by the morbillivirus Peste des petits ruminants virus (PPRV), which is closely related to Rinderpest virus (RPV), Canine distemper virus (CDV) and Measles virus (MeV)

  • We tested whether infection with PPRV stimulated the production of IFN-β, using PPRV-infected Vero-human-SLAM (VHS) cells which had previously been transfected with a reporter plasmid expressing luciferase under the control of the IFN-β promoter and a transfection control plasmid constitutively expressing β-galactosidase

  • We tested the effect of infection with the PPRV vaccine strain (Nigeria/75/1) [54], using a recombinant version [55], which we used in later experiments to introduce mutations into PPRV; we observed that this virus failed to activate the IFN-β promoter (Fig 1D)

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Summary

Introduction

Peste des petits ruminants (PPR) is a viral disease of sheep, goats and related wild animals. It is caused by the morbillivirus Peste des petits ruminants virus (PPRV), which is closely related to Rinderpest virus (RPV), Canine distemper virus (CDV) and Measles virus (MeV). PPRV is widely distributed in the African and Asian continents (see [1] for a recent review), and it can be classified in four genetic lineages based on the sequence of short segments of either the F or the N genes [2,3,4]. All four lineages share the same serotype, and a single vaccine strain, based on a Nigerian isolate, has provided complete protection against disease from West Africa to China. The severity of the clinical signs, from mild to severe, varies with the virus isolate and with the host [10,11,12,13]

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