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Publication . Article . 2021

Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses

Parej Nath; Nishant Ranjan Chauhan; Kautilya Kumar Jena; Ankita Datey; Nilima Dinesh Kumar; Subhash Mehto; Saikat De; +11 Authors
Open Access
English
Published: 04 Nov 2021 Journal: EMBO Reports, volume 22, issue 11 (issn: 1469-221X, eissn: 1469-3178, Copyright policy )
Publisher: John Wiley and Sons Inc.
Country: Netherlands
Abstract
Abstract The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear. In this study, we show that IRGM expression is increased upon viral infection. IFN responses induced by viral PAMPs are negatively regulated by IRGM. Conversely, IRGM depletion results in a robust induction of key viral restriction factors including IFITMs, APOBECs, SAMHD1, tetherin, viperin, and HERC5/6. Additionally, antiviral processes such as MHC‐I antigen presentation and stress granule signaling are enhanced in IRGM‐deficient cells, indicating a robust cell‐intrinsic antiviral immune state. Consistently, IRGM‐depleted cells are resistant to the infection with seven viruses from five different families, including Togaviridae, Herpesviridae, Flaviviverdae, Rhabdoviridae, and Coronaviridae. Moreover, we show that Irgm1 knockout mice are highly resistant to chikungunya virus (CHIKV) infection. Altogether, our work highlights IRGM as a broad therapeutic target to promote defense against a large number of human viruses, including SARS‐CoV‐2, CHIKV, and Zika virus.
IRGM negatively regulates IFN responses and IRGM expression is increased upon viral infection. Its depletion triggers anti‐viral restriction factors and promotes resistance to a large number of human viruses, including SARS‐CoV2, CHIKV and ZIKV.
Subjects by Vocabulary

Medical Subject Headings: viruses

Microsoft Academic Graph classification: Rhabdoviridae biology.organism_classification biology Virology Interferon medicine.drug medicine Coronaviridae Tetherin Viperin Viral replication IRGM Virus

Subjects

Report, Reports, IRGM, IRGM1, CHIKV, ZIKV, SARS‐CoV‐2, Immunology, Microbiology, Virology & Host Pathogen Interaction, Signal Transduction, Genetics, Molecular Biology, Biochemistry

Funded by
EC| PRONKJEWAIL
Project
PRONKJEWAIL
Protecting patients with enhanced susceptibility to infections
  • Funder: European Commission (EC)
  • Project Code: 713660
  • Funding stream: H2020 | MSCA-COFUND-DP
Validated by funder
Related to Research communities
COVID-19
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