» Articles » PMID: 30201512

A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation

Overview
Date 2018 Sep 12
PMID 30201512
Citations 135
Authors
Affiliations
Soon will be listed here.
Abstract

Induction of interferons during viral infection is mediated by cellular proteins that recognise viral nucleic acids. MDA5 is one such sensor of virus presence and is activated by RNA. MDA5 is required for immunity against several classes of viruses, including picornaviruses. Recent work showed that mutations in the IFIH1 gene, encoding MDA5, lead to interferon-driven autoinflammatory diseases. Together with observations made in cancer cells, this suggests that MDA5 detects cellular RNAs in addition to viral RNAs. It is therefore important to understand the properties of the RNAs which activate MDA5. New data indicate that RNA length and secondary structure are features sensed by MDA5. We review these developments and discuss how MDA5 strikes a balance between antiviral immunity and autoinflammation.

Citing Articles

Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing.

Zheng D, Li X, Wang P, Zhu Q, Huang Z, Zhao T Front Immunol. 2025; 15():1440922.

PMID: 39845969 PMC: 11752880. DOI: 10.3389/fimmu.2024.1440922.


An MST-based assay reveals new binding preferences of IFIT1 for canonically and noncanonically capped RNAs.

Spiewla T, Grab K, Depaix A, Ziemkiewicz K, Warminski M, Jemielity J RNA. 2024; 31(2):181-192.

PMID: 39643445 PMC: 11789485. DOI: 10.1261/rna.080089.124.


Apoptotic Caspases Suppress Expression of Endogenous Retroviruses in HPV31+ Cells That Are Associated with Activation of an Innate Immune Response.

Studstill C, Huang N, Sundstrom S, Moscoso S, Zhang H, Damania B Viruses. 2024; 16(11).

PMID: 39599810 PMC: 11598866. DOI: 10.3390/v16111695.


UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling.

Harrison A, Yang D, Cahoon J, Geng T, Cao Z, Karginov T Nat Immunol. 2024; 25(12):2234-2246.

PMID: 39567760 DOI: 10.1038/s41590-024-02004-7.


Comprehensive Enteroviral Serology Links Infection and Anti-Melanoma Differentiation-Associated Protein 5 Dermatomyositis.

Jayaraman S, Tiniakou E, Morgenlander W, Na M, Christopher-Stine L, Larman H ACR Open Rheumatol. 2024; 7(1):e11752.

PMID: 39509140 PMC: 11694254. DOI: 10.1002/acr2.11752.


References
1.
Dou Y, Yim H, Kirkwood C, Williams B, Sadler A . The innate immune receptor MDA5 limits rotavirus infection but promotes cell death and pancreatic inflammation. EMBO J. 2017; 36(18):2742-2757. PMC: 5599799. DOI: 10.15252/embj.201696273. View

2.
Volkman H, Stetson D . The enemy within: endogenous retroelements and autoimmune disease. Nat Immunol. 2014; 15(5):415-22. PMC: 4131434. DOI: 10.1038/ni.2872. View

3.
Hertzog J, Dias Junior A, Rigby R, Donald C, Mayer A, Sezgin E . Infection with a Brazilian isolate of Zika virus generates RIG-I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signaling. Eur J Immunol. 2018; 48(7):1120-1136. PMC: 6055886. DOI: 10.1002/eji.201847483. View

4.
Yan N, Chen Z . Intrinsic antiviral immunity. Nat Immunol. 2012; 13(3):214-22. PMC: 3549670. DOI: 10.1038/ni.2229. View

5.
Ramaswami G, Li J . RADAR: a rigorously annotated database of A-to-I RNA editing. Nucleic Acids Res. 2013; 42(Database issue):D109-13. PMC: 3965033. DOI: 10.1093/nar/gkt996. View