Abstract
Peste des petits ruminants virus (PPRV) is associated with global peste des petits ruminants resulting in severe economic loss. Peste des petits ruminants virus dampens host interferon-based signaling pathways through multiple mechanisms. Previous studies deciphered the role of V and C in abrogating IFN-β production. Moreover, V protein directly interacted with signal transducers and activators of transcription 1 (STAT1) and STAT2 resulting in the impairment of host IFN responses. In our present study, PPRV infection inhibited both IFN-β- and IFN-γ-induced activation of IFN-stimulated response element (ISRE) and IFN-γ-activated site (GAS) element, respectively. Both N and P proteins, functioning as novel IFN response antagonists, markedly suppressed IFN-β-induced ISRE and IFN-γ-induced GAS promoter activation to impair downstream upregulation of various interferon-stimulated genes (ISGs) and prevent STAT1 nuclear translocation. Specifically, P protein interacted with STAT1 and subsequently inhibited STAT1 phosphorylation, whereas N protein neither interacted with STAT1 nor inhibited STAT1 phosphorylation as well as dimerization, suggesting that the N and P protein antagonistic effects were different. Though they differed in their relationship to STAT1, both proteins blocked JAK-STAT signaling, severely negating the host antiviral immune response. Our study revealed a new mechanism employed by PPRV to evade host innate immune response, providing a platform to study the interaction of paramyxoviruses and host response.
Highlights
Peste des petits ruminants (PPR), a severe contagious viral disease of domestic and wild small ruminants, affects goats and sheep [1]
To identify the viral proteins that were responsible for the peste des petits ruminants virus (PPRV)-mediated antagonistic role against IFN-β- and IFN-γ-induced response, the plasmids expressing various viral proteins were co-transfected with IFN-stimulated response element (ISRE) or gamma interferon activated site (GAS) reporter plasmids, and the cells were mock-treated or treated with IFN-β and IFN-γ
The M protein failed to inhibit ISRE or GAS promoter activation (Figure 1C,D). These results indicate that PPRV N and P proteins play an antagonistic role against both IFN-β- and IFN-γ-induced IFN response
Summary
Peste des petits ruminants (PPR), a severe contagious viral disease of domestic and wild small ruminants, affects goats and sheep [1]. The disease was first reported in the Ivory Coast area of West Africa in 1942 [2]. PPR has markedly spread from the Ivory Coast to numerous other regions, including countries in Africa, the Middle East, Asia, and Europe [3,4,5,6]. PPR represents a global threat to about 62.5% of goat and sheep populations and is considered by the goat and sheep industry to be an economically important infectious disease worldwide [7]. The causative agent of PPR, peste des petits ruminants virus (PPRV), belongs to the genus. Peste des petits ruminants virus is a non-segmented, Viruses 2019, 11, 629; doi:10.3390/v11070629 www.mdpi.com/journal/viruses
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