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

Abstract

The mitochondrial antiviral-signaling protein (MAVS, also known as VISA, IPS-1, or CARDIF) plays an essential role in the type I interferon (IFN) response and in retinoic acid-inducible gene I (RIG-I) mediated antiviral innate immunity in mammals. In this study, the caprine MAVS gene (caMAVS, 1566 bp) was identified and cloned. The caMAVS shares the highest amino acid similarity (98.1%) with the predicted sheep MAVS. Confocal microscopy analysis of partial deletion mutants of caMAVS revealed that the transmembrane and the so-called Non-Characterized domains are indispensable for intracellular localization to mitochondria. Overexpression of caMAVS in caprine endometrial epithelial cells up-regulated the mRNA levels of caprine interferon-stimulated genes. We concluded that caprine MAVS mediates the activation of the type I IFN pathway. We further demonstrated that both the CARD-like domain and the transmembrane domain of caMAVS were essential for the activation of the IFN-β promotor. The interaction between caMAVS and caprine RIG-I and the vital role of the CARD and NC domain in this interaction was demonstrated by co-immunoprecipitation. Upon infection with the Peste des Petits Ruminants Virus (PPRV, genus Morbillivirus), the level of MAVS was greatly reduced. This reduction was prevented by the addition of the proteasome inhibitor MG132. Moreover, we found that viral protein V could interact and colocalize with MAVS. Together, we identified caMAVS as a RIG-I interactive protein involved in the activation of type I IFN pathways in caprine cells and as a target for PPRV immune evasion.

Peste des Petits Ruminants virus virulence is associated with an early inflammatory profile in the tonsils and cell cycle arrest in lymphoid tissue

“…The inflammation observed in MA08-infected animals may also be linked to protein expression, as a core set of inflammatory proteins was expressed in PBMCs. In this context, this strain is able to use all the mechanisms described elsewhere that are involved in PPRV virulence [39,17,19,[40][41][42][43].…”

Peste des petits ruminants virus non-structural V and C proteins interact with the NF-κB p65 subunit and modulate pro-inflammatory cytokine gene induction

“…In addition, PPRV-V protein has been shown to interact with STAT1 and STAT2, thereby blocking IFN signalling by disrupting the JAK-STAT signalling cascade [16]. The paramyxoviruses have been reported to evade the antiviral state by altering the transcriptional activation of IRF-3 and NF-κB [12,33,[47][48][49]. Viruses exploit diverse strategies to modulate the NF-κB pathway for their efficient replication and survival as observed with some paramyxoviruses including measles virus, sendai virus and respiratory syncytial virus [32,37,50].…”

Research Progress on Emerging Viral Pathogens of Small Ruminants in China during the Last Decade

“…Previous studies have documented crucial roles for viral proteins in blocking type I and type II IFN responses, and various mechanisms have been proposed for these effects. Upon PPRV infection, mitochondrial antiviral-signaling protein (MAVS, also known as VISA, IPS-1, or CARDIF) plays an essential role in the activation of the type I IFN pathway [20]. PPRV infection significantly induces ATG13 (autophagy-related 13) expression, and ATG13 exerts an obvious antiviral effect on PPRV infection in vitro [21].…”