ArticleCell death & disease2020
MDA5 cleavage by the Leader protease of foot-and-mouth disease virus reveals its pleiotropic effect against the host antiviral response.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Establishing the molecular basis for MDA5 mutation-linked autoimmunity.Nucleic acids research · 2026Article
- The assembly of stress granules during foot-and-mouth disease virus infection is uncoupled from activation of cellular intrinsic antiviral signalling.PLoS pathogens · 2026Article
- The La Region of Foot-and-Mouth Disease Virus: Essential for L Protein Cellular Distribution but Not Functional Activity.International journal of molecular sciences · 2026Article
- Foot-and-mouth disease virus 3D polymerase antagonizes the interferon signaling pathway by blocking STAT2 nuclear translocation.Virus research · 2026Article
- Dicer is cleaved by the Leader protease encoded by foot-and-mouth disease virus to promote infection in mammalian cells.Science advances · 2025Article
- DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2025Review
- HCoV-229E Mpro Suppresses RLR-Mediated Innate Immune Signalling Through Cleavage of NEMO and Through Other Mechanisms.International journal of molecular sciences · 2025Article
- Review
- The antiviral response triggered by the cGAS/STING pathway is subverted by the foot-and-mouth disease virus proteases.Cellular and molecular life sciences : CMLS · 2024Article
- Host-Specific Interplay between Foot-and-Mouth Disease Virus 3D Polymerase and the Type-I Interferon Pathway.Viruses · 2023Article
- The Foot-and-Mouth Disease Virus Lb Protease Cleaves Intracellular Transcription Factors STAT1 and STAT2 to Antagonize IFN-β-Induced Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Foot-and-Mouth Disease Virus: Molecular Interplays with IFN Response and the Importance of the Model.Viruses · 2022Review
- Seneca Valley Virus Induces DHX30 Cleavage to Antagonize Its Antiviral Effects.Journal of virology · 2022Article
- Surgical Strikes on Host Defenses: Role of the Viral Protease Activity in Innate Immune Antagonism.Pathogens (Basel, Switzerland) · 2022Review
- Inhibition of Antiviral Innate Immunity by Foot-and-Mouth Disease Virus LJournal of virology · 2021Article
- Uncovering targets of the Leader protease: Linking RNA-mediated pathways and antiviral defense.Wiley interdisciplinary reviews. RNA · 2021Review
- RNA-Binding Proteins at the Host-Pathogen Interface Targeting Viral Regulatory Elements.Viruses · 2021Article
- Picornaviruses: A View from 3A.Viruses · 2021Review
- Article
- Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV.Frontiers in microbiology · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The RIG-I-like receptor (RLR) melanoma differentiation-associated gene 5 (MDA5) plays a key role in triggering innate antiviral response during infection by RNA viruses. MDA5 activation leads to transcription induction of type-I interferon (IFN) and proinflammatory cytokines. MDA5 has also been associated with autoimmune and autoinflammatory diseases by dysfunctional activation of innate immune response in the absence of infection. Here, we show how foot-and-mouth disease virus (FMDV) counteracts the specific antiviral effect exerted by MDA5 targeting the protein for cleavage by the viral Leader protease (Lpro). MDA5 overexpression had an inhibitory effect on FMDV infection in IFN-competent cells. Remarkably, immunostimulatory viral RNA co-immunoprecipitated with MDA5 in infected cells. Moreover, specific cleavage of MDA5 by Lpro was detected in co-transfected cells, as well as during the course of FMDV infection. A significant reduction in IFN induction associated with MDA5 cleavage was detected by comparison with a non-cleavable MDA5 mutant protein with preserved antiviral activity. The Lpro cleavage site in MDA5 was identified as the RGRAR sequence in the conserved helicase motif VI, coinciding with that recently reported for Lpro in LGP2, another member of the RLRs family involved in antiviral defenses. Interestingly, specific mutations within the MDA5 Lpro target sequence have been associated with immune disease in mice and humans. Our results reveal a pleiotropic strategy for immune evasion based on a viral protease targeting phylogenetically conserved domains of immune sensors. Identification of viral strategies aimed to disrupt MDA5 functionality may also contribute to develop new treatment tools for MDA5-related disorders.
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