TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.

Encapsidation is a strategy almost universally employed by viruses to protect their genomes from degradation and from innate immune sensors. We show that TRIM21, which targets antibody-opsonized virions for proteasomal destruction, circumvents this protection, enabling the rapid detection and degrad...

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Main Authors: Ruth E Watkinson, William A McEwan, Jerry C H Tam, Marina Vaysburd, Leo C James
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-10-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005253&type=printable
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author Ruth E Watkinson
William A McEwan
Jerry C H Tam
Marina Vaysburd
Leo C James
author_facet Ruth E Watkinson
William A McEwan
Jerry C H Tam
Marina Vaysburd
Leo C James
author_sort Ruth E Watkinson
collection DOAJ
description Encapsidation is a strategy almost universally employed by viruses to protect their genomes from degradation and from innate immune sensors. We show that TRIM21, which targets antibody-opsonized virions for proteasomal destruction, circumvents this protection, enabling the rapid detection and degradation of viral genomes before their replication. TRIM21 triggers an initial wave of cytokine transcription that is antibody, rather than pathogen, driven. This early response is augmented by a second transcriptional program, determined by the nature of the infecting virus. In this second response, TRIM21-induced exposure of the viral genome promotes sensing of DNA and RNA viruses by cGAS and RIG-I. This mechanism allows early detection of an infection event and drives an inflammatory response in mice within hours of viral challenge.
format Article
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institution OA Journals
issn 1553-7366
1553-7374
language English
publishDate 2015-10-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Pathogens
spelling doaj-art-b86ace7174324237b3feeb9bbf05ff472025-08-20T02:22:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-10-011110e100525310.1371/journal.ppat.1005253TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.Ruth E WatkinsonWilliam A McEwanJerry C H TamMarina VaysburdLeo C JamesEncapsidation is a strategy almost universally employed by viruses to protect their genomes from degradation and from innate immune sensors. We show that TRIM21, which targets antibody-opsonized virions for proteasomal destruction, circumvents this protection, enabling the rapid detection and degradation of viral genomes before their replication. TRIM21 triggers an initial wave of cytokine transcription that is antibody, rather than pathogen, driven. This early response is augmented by a second transcriptional program, determined by the nature of the infecting virus. In this second response, TRIM21-induced exposure of the viral genome promotes sensing of DNA and RNA viruses by cGAS and RIG-I. This mechanism allows early detection of an infection event and drives an inflammatory response in mice within hours of viral challenge.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005253&type=printable
spellingShingle Ruth E Watkinson
William A McEwan
Jerry C H Tam
Marina Vaysburd
Leo C James
TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.
PLoS Pathogens
title TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.
title_full TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.
title_fullStr TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.
title_full_unstemmed TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.
title_short TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.
title_sort trim21 promotes cgas and rig i sensing of viral genomes during infection by antibody opsonized virus
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005253&type=printable
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