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, Tapas Kumar Nayak, Swatismita Priyadarsini, Kshitish Rout, Ramyasingh Bal, Krushna C Murmu, Manjula Kalia, Srinivas Patnaik, Punit Prasad, Fulvio Reggiori, Soma Chattopadhyay*, Santosh Chauhan*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

5 Citaten (Scopus)
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Samenvatting

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.

Originele taal-2English
Artikelnummere52948
Aantal pagina's17
TijdschriftEmbo Reports
Volume22
Nummer van het tijdschrift11
Vroegere onlinedatum1-sep-2021
DOI's
StatusPublished - 4-nov-2021

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