Abstract
Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease in domestic and wild small ruminants throughout the world, mainly by invoking immunosuppression in its natural hosts. It has been suggested that the non-structural C protein of PPRV helps in evading host responses but the molecular mechanisms by which it antagonizes the host responses have not been fully characterized. Here, we report the antagonistic effect of PPRV C protein on the expression of interferon-β (IFN-β) through both MAVS and RIG-I mediated pathways in vitro. Dual luciferase reporter assay and direct expression of IFN-β mRNA analysis indicated that PPRV C significantly down regulates IFN-β via its potential interaction with MAVS and RIG-I signaling molecules. Results further indicated that PPRV C protein significantly suppresses endogenous and exogenous IFN-β-induced anti-viral effects in PPRV, EMCV and SVS infections in vitro. Moreover, PPRV C protein not only down regulates IFN-β but also the downstream cytokines of interferon stimulated genes 56 (ISG56), ISG15, C-X-C motif chemokine (CXCL10) and RIG-I mediated activation of IFN promoter elements of ISRE and NF-κB. Further, this study deciphers that PPRV C protein could significantly inhibit the phosphorylation of STAT1 and interferes with the signal transmission in JAK-STAT signaling pathway. Collectively, this study indicates that PPRV C protein is important for innate immune evasion and disease progression.
Highlights
Peste des petits ruminants (PPR) is an acute and highly contagious disease of both domestic and wild small ruminants, caused by peste des petits ruminants virus (PPRV), a Morbillivirus of the Paramyxoviridae family [1]
Western blot (WB) was performed to determine the expressions of PPRV C and Retinoic acid-inducible gene I (RIG-I) proteins when pCMV-HA-C and pRK-Flag-RIG-IN were co-transfected into HEK-293T cells (Fig. 1a)
Dual luciferase reporter assay was performed to detect whether PPRV C protein affects the activities of IFN-β and its downstream IFN stimulated response element (ISRE) and nuclear factor kappa-B (NF-κB)
Summary
Peste des petits ruminants (PPR) is an acute and highly contagious disease of both domestic and wild small ruminants, caused by peste des petits ruminants virus (PPRV), a Morbillivirus of the Paramyxoviridae family [1]. Viruses are able to use various strategies to evade the immune responses including the induction of immunosuppression by offsetting host IFN responses, stimulated via pathogen-associated molecular patterns (PAMPs) by cellular pathogen recognition receptors (PRRs). The two tandem caspase recruitment domains (CARDs) at the amino-termini of MDA-5 and RIG-I are presumed to have a role in the downstream signaling which activates IFN-β promoter [13]. LGP2, lacking CARD, on the other hand, activates and represses MDA-5 and RIG-1, respectively [14,15,16]. LGP2 role in PAMP recognition by MDA-5 and RIG-I has been suggested [17]
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