Cell-type specificity and functional redundancy of RIG-I-like receptors in innate immune sensing of Coxsackievirus B3 and encephalomyocarditis virus

• Type of Material: Article
• Authors: Eesther Francisco, Columbia University; Mehul Suthar, Emory University; Michael Gale, Jr., University of Washington; Amy B. Rosenfeld, Columbia University; Vincent R. Racaniello, Columbia University
• Language: English
• Date: 2019-02-01
• Publisher: Academic Press Inc. & Elsevier Science
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2018.12.003
• Title of Journal or Parent Work: Virology
• Volume: 528
• Start Page: 7
• End Page: 18
• Grant/Funding Information: This work was supported in part by Public Health Service Grants AI50754, AI139775, AI118916, and AI127463 from the National Institute of Allergy and Infectious Diseases.
• Keywords: Picornavirus; RNA recognition; Antiviral responses; Protein; Activation; Identification; RIG-I; Science & Technology; Virology; Induction; Macrophage; Genes; Interferon; Innate immunity; Life Sciences & Biomedicine; MDA5; Replication
• Research Categories: Biology, Genetics; Health Sciences, Immunology; Biology, Virology

Abstract

The contributions of RIG-I and MDA5 receptors to sensing viruses of the Picornaviridae family were investigated. The picornaviruses encephalomyocarditis virus (EMCV) and Coxsackievirus B3 (CVB3) are detected by both MDA5 and RIG-I in bone marrow derived macrophages. In macrophages from wild type mice, type I IFN is produced early after infection; IFNβ synthesis is reduced in the absence of each sensor, while IFNα production is reduced in the absence of MDA5. EMCV and CVB3 do not replicate in murine macrophages, and their detection is different in murine embryonic fibroblasts (MEFs), in which the viruses replicate to high titers. In MEFs RIG-I was essential for the expression of type I IFNs but contributes to increased yields of CVB3, while MDA5 inhibited CVB3 replication but in an IFN independent manner. These observations demonstrate functional redundancy within the innate immune response to picornaviruses.