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Published on: March 2, 2014
Caprine MAVS Is a RIG-I Interacting Type I Interferon Inducer Downregulated by Peste des Petits Ruminants Virus
Qiuhong Miao1,2, Ruibing Qi1, Chunchun Meng1
1Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai 200241, China.
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.
Insights
The caprine MAVS protein is crucial for activating antiviral immunity in goats. Peste des Petits Ruminants Virus (PPRV) degrades MAVS to evade immunity, highlighting MAVS as a potential therapeutic target.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Mitochondrial antiviral-signaling protein (MAVS) is essential for innate antiviral immunity in mammals.
- MAVS mediates the retinoic acid-inducible gene I (RIG-I) signaling pathway, crucial for type I interferon responses.
- Understanding caprine MAVS is vital for controlling viral diseases in goats.
Purpose of the Study:
- To identify and characterize the caprine MAVS (caMAVS) gene.
- To investigate the role of caMAVS in type I interferon pathway activation.
- To explore the interaction between caMAVS and Peste des Petits Ruminants Virus (PPRV).
Main Methods:
- Gene cloning and sequencing of caMAVS.
- Confocal microscopy to determine protein localization.
- Quantitative PCR to measure gene expression.
- Co-immunoprecipitation assays to study protein interactions.
- Proteasome inhibitor treatment to assess MAVS degradation.
Main Results:
- The caMAVS gene was cloned and shares high similarity with sheep MAVS.
- Transmembrane and Non-Characterized domains are essential for mitochondrial localization.
- caMAVS activates type I interferon-stimulated genes and the IFN-β promoter.
- caMAVS interacts with caprine RIG-I, with CARD and NC domains being critical.
- PPRV infection reduces caMAVS levels via proteasomal degradation, involving viral protein V.
Conclusions:
- Caprine MAVS is a key mediator of type I interferon antiviral responses in goats.
- Specific domains of caMAVS are critical for its function and localization.
- PPRV utilizes viral protein V to degrade caMAVS, facilitating immune evasion.
- caMAVS is a potential target for developing strategies against PPRV infection.
