Peste des petits ruminants virus non-structural C protein inhibits the induction of interferon-β by potentially interacting with MAVS and RIG-I

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.

Extracellular vesicles derived from PPRV-infected cells enhance signaling lymphocyte activation molecular (SLAM) receptor expression and facilitate virus infection

“…Mock- and PPRV-infected cells were used as negative and positive control, respectively. Our data showed that PPRV infection significantly suppressed alpha interferon (IFN-α) ( Fig 6A ) and gamma interferon (IFN-γ) ( Fig 6B ) expression, while stimulated expressionof tumor necrosis factor α (TNF-α) ( Fig 6C ), interleukin 4 (IL-4) ( Fig 6D ), and interleukin 10 (IL-10) ( Fig 6E ) as previously described [ 11 , 16 , 42 – 44 ]. Similar effects of EVs-PPRV or EVs-pcDNA3.1-H on the expression of these cytokines by the recipient cells compared to that of respective control was detected ( Fig 6A–6E ).…”

“…Mock-and PPRV-infected cells were used as negative and positive control, respectively. Our data showed that PPRV infection significantly suppressed alpha interferon (IFN-α) (Fig 6A [11,16,[42][43][44]. Similar effects of EVs-PPRV or EVs-pcDNA3.1-H on the expression of these cytokines by the recipient cells compared to that of respective control was detected (Fig 6A -6E).…”

Type I and Type II Interferon Antagonism Strategies Used by Paramyxoviridae: Previous and New Discoveries, in Comparison

“…PPRV C protein wasn’t able to bind MDA-5 and RIG-I, but PPRV lacking C protein expression lost the ability to block both MDA-5 and RIG-I mediated IFN induction [ 175 ]. A recent paper confirmed that C protein of PPRV blocks RIG-I or MAVS mediated IFN β reporter activation [ 176 ]. Interestingly, using C protein from different genera, in particular SeV, bPIV3, MeV, and NiV C proteins, Yamaguchi et al showed that all the C proteins bind to IKKα and inhibit IRF7 phosphorylation, and thus block toll-like receptor (TLR) 7- and TLR9-dependent IFN-α induction, which is a hallmark of activation of plasmacytoid dendritic cells ( Figure 2 ) [ 115 ].…”

Caprine MAVS Is a RIG-I Interacting Type I Interferon Inducer Downregulated by Peste des Petits Ruminants Virus Infection

“…Although we did observe co-localization of PPRV-V with caMAVS in transfected cells, further studies will be required to fully understand the degradative interplay between PPRV-V and caMAVS. Interestingly, PPRV-C protein has recently been demonstrated to inhibit IFN-β induction by interacting with RIG-I and MAVS [44], which might indicate that both PPRV-V and PPRV-C are critical for counteracting the innate immune response. Since the results described in this study are based on the PPRV vaccine strain from lineage II, it would be interesting to follow up on this research to investigate commonalities and potential differences between the four circulating lineages [45] in their ability to counteract caMAVS.…”