Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses.
EMBO Rep
; 22(11): e52948, 2021 11 04.
Article
in English
| MEDLINE | ID: covidwho-1381494
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Diseases
/
GTP-Binding Proteins
Limits:
Animals
/
Humans
Language:
English
Journal:
EMBO Rep
Journal subject:
Molecular Biology
Year:
2021
Document Type:
Article
Affiliation country:
Embr.202152948
Similar
MEDLINE
...
LILACS
LIS