Control of the induction of type I interferon by Peste des petits ruminants virus

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.

Early transcriptome profile of goat peripheral blood mononuclear cells (PBMCs) infected with peste des petits ruminant's vaccine virus (Sungri/96) revealed induction of antiviral response in an interferon independent manner

“…Interestingly, in our study type I interferons (IFN-α and IFN-β) were not differentially expressed, although, interferon induced genes were found to be induced. This supports the recent observation that the paramyxovirus (including PPRV) non-structural proteins (C and V proteins) play a role in inhibiting type I IFN production (Bernardo et al, 2017;Andrejeva et al, 2004). In the present study, at 6 h p.i.…”

“…Recently, PPRV V protein was found to bind MDA-5 and its overexpression was shown to block IFN-β pathways (Bernardo et al, 2017). Previous transcriptome studies in our laboratory highlighted induction of robust antiviral response in an interferon independent manner at 48 h and 120 h post infection (p.i.)…”

“…Thus, interferon stimulated genes (ISGs) along with other cytokines and chemokines help in establishing an antiviral state in infected host cells. Interestingly, few RNA viruses including PPRV, have developed unique mechanisms to counterattack the host interferon (IFN) responses by subverting the host interferon signaling and thus, establish infection evading host innate and adaptive immune defenses (Bernardo et al, 2017;Nanda and Baron., 2006;Pauli et al, 2008;Nan et al, 2014).…”

MicroRNA-1 Negatively Regulates Peripheral NK Cell Function via Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Signaling Pathways During PPRV Infection

“…Studies available on the induction of both type I-and type II-interferon (IFN) during PPRV infection in vivo or after vaccination are inconclusive (28)(29)(30)(31)(32). Indeed, it has been shown that PPRV infection alone was sufficient to cause the decrease of IFN-γ production and suppression of IFN-γ activation in infected cells, including Vero cells and goat fibroblasts (28,31,32). This implicates a role for either PPRV itself or cellular factors regulated by PPRV replication in impairing IFN-γproducing cells and contributing to viral persistence.…”

“…This implicates a role for either PPRV itself or cellular factors regulated by PPRV replication in impairing IFN-γproducing cells and contributing to viral persistence. At early PPRV infection, NK cells are considered as the primary source of IFN-γ (28,32). However, it remains largely unknown how NK cells respond and are regulated at the earliest time points after an acute viral PPRV infection in goats.…”