The P150 Isoform of ADAR1 Blocks Sustained RLR Signaling and Apoptosis During Influenza Virus Infection

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2020 Sep 8

PMID 32898178

Citations 18

Authors

Olivia A Vogel

Julianna Han

Chieh-Yu Liang

Santhakumar Manicassamy

Jasmine T Perez

Balaji Manicassamy

Affiliations

Soon will be listed here.

Abstract

Signaling through retinoic acid inducible gene I (RIG-I) like receptors (RLRs) is tightly regulated, with activation occurring upon sensing of viral nucleic acids, and suppression mediated by negative regulators. Under homeostatic conditions aberrant activation of melanoma differentiation-associated protein-5 (MDA5) is prevented through editing of endogenous dsRNA by RNA editing enzyme Adenosine Deaminase Acting on RNA (ADAR1). In addition, ADAR1 is postulated to play pro-viral and antiviral roles during viral infections that are dependent or independent of RNA editing activity. Here, we investigated the importance of ADAR1 isoforms in modulating influenza A virus (IAV) replication and revealed the opposing roles for ADAR1 isoforms, with the nuclear p110 isoform restricting versus the cytoplasmic p150 isoform promoting IAV replication. Importantly, we demonstrate that p150 is critical for preventing sustained RIG-I signaling, as p150 deficient cells showed increased IFN-β expression and apoptosis during IAV infection, independent of RNA editing activity. Taken together, the p150 isoform of ADAR1 is important for preventing sustained RIG-I induced IFN-β expression and apoptosis during viral infection.

Citing Articles

ADAR1 Promotes NUPR1 A-to-I RNA Editing to Exacerbate Ischemic Brain Injury by Microglia Mediated Neuroinflammation.

Wang G, Li W, Li Y, Ma M, Guo K Neuromolecular Med. 2025; 27(1):16.

PMID: 40009287 DOI: 10.1007/s12017-025-08841-5.

CRISPR editing of candidate host factors that impact influenza A virus infection.

Kyawe P, Liu P, Jiang Z, Bradley E, Cicuto T, Trombly M Microbiol Spectr. 2025; 13(3):e0262724.

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Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape.

An W, Lakhina S, Leong J, Rawat K, Husain M Pathogens. 2024; 13(7).

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ADAR1 promotes cisplatin resistance in intrahepatic cholangiocarcinoma by regulating BRCA2 expression through A-to-I editing manner.

Liu Q, Huang C, Chen S, Zhu Y, Huang X, Zhao G Cell Prolif. 2024; 57(10):e13659.

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RNA editing and immune control: from mechanism to therapy.

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