Cargando…

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

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 vi...

Descripción completa

Detalles Bibliográficos
Autores principales: Nath, Parej, Chauhan, Nishant Ranjan, Jena, Kautilya Kumar, Datey, Ankita, Kumar, Nilima Dinesh, Mehto, Subhash, De, Saikat, Nayak, Tapas Kumar, Priyadarsini, Swatismita, Rout, Kshitish, Bal, Ramyasingh, Murmu, Krushna C, Kalia, Manjula, Patnaik, Srinivas, Prasad, Punit, Reggiori, Fulvio, Chattopadhyay, Soma, Chauhan, Santosh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567234/
https://www.ncbi.nlm.nih.gov/pubmed/34467632
http://dx.doi.org/10.15252/embr.202152948
_version_ 1784594189151895552
author Nath, Parej
Chauhan, Nishant Ranjan
Jena, Kautilya Kumar
Datey, Ankita
Kumar, Nilima Dinesh
Mehto, Subhash
De, Saikat
Nayak, Tapas Kumar
Priyadarsini, Swatismita
Rout, Kshitish
Bal, Ramyasingh
Murmu, Krushna C
Kalia, Manjula
Patnaik, Srinivas
Prasad, Punit
Reggiori, Fulvio
Chattopadhyay, Soma
Chauhan, Santosh
author_facet Nath, Parej
Chauhan, Nishant Ranjan
Jena, Kautilya Kumar
Datey, Ankita
Kumar, Nilima Dinesh
Mehto, Subhash
De, Saikat
Nayak, Tapas Kumar
Priyadarsini, Swatismita
Rout, Kshitish
Bal, Ramyasingh
Murmu, Krushna C
Kalia, Manjula
Patnaik, Srinivas
Prasad, Punit
Reggiori, Fulvio
Chattopadhyay, Soma
Chauhan, Santosh
author_sort Nath, Parej
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8567234
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-85672342021-11-12 Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses Nath, Parej Chauhan, Nishant Ranjan Jena, Kautilya Kumar Datey, Ankita Kumar, Nilima Dinesh Mehto, Subhash De, Saikat Nayak, Tapas Kumar Priyadarsini, Swatismita Rout, Kshitish Bal, Ramyasingh Murmu, Krushna C Kalia, Manjula Patnaik, Srinivas Prasad, Punit Reggiori, Fulvio Chattopadhyay, Soma Chauhan, Santosh EMBO Rep Reports 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. John Wiley and Sons Inc. 2021-09-01 2021-11-04 /pmc/articles/PMC8567234/ /pubmed/34467632 http://dx.doi.org/10.15252/embr.202152948 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reports
Nath, Parej
Chauhan, Nishant Ranjan
Jena, Kautilya Kumar
Datey, Ankita
Kumar, Nilima Dinesh
Mehto, Subhash
De, Saikat
Nayak, Tapas Kumar
Priyadarsini, Swatismita
Rout, Kshitish
Bal, Ramyasingh
Murmu, Krushna C
Kalia, Manjula
Patnaik, Srinivas
Prasad, Punit
Reggiori, Fulvio
Chattopadhyay, Soma
Chauhan, Santosh
Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses
title Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses
title_full Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses
title_fullStr Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses
title_full_unstemmed Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses
title_short Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses
title_sort inhibition of irgm establishes a robust antiviral immune state to restrict pathogenic viruses
topic Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567234/
https://www.ncbi.nlm.nih.gov/pubmed/34467632
http://dx.doi.org/10.15252/embr.202152948
work_keys_str_mv AT nathparej inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT chauhannishantranjan inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT jenakautilyakumar inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT dateyankita inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT kumarnilimadinesh inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT mehtosubhash inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT desaikat inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT nayaktapaskumar inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT priyadarsiniswatismita inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT routkshitish inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT balramyasingh inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT murmukrushnac inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT kaliamanjula inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT patnaiksrinivas inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT prasadpunit inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT reggiorifulvio inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT chattopadhyaysoma inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses
AT chauhansantosh inhibitionofirgmestablishesarobustantiviralimmunestatetorestrictpathogenicviruses