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...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2015-10, Vol.11 (10), p.e1005253-e1005253
Main Authors: Watkinson, Ruth E, McEwan, William A, Tam, Jerry C H, Vaysburd, Marina, James, Leo C
Format: Article
Language:English
Subjects:
Adenovirus Infections, Human - immunology
Adenoviruses
Analysis
Animals
Cellular signal transduction
Councils
Cytokines
DEAD Box Protein 58
DEAD-box RNA Helicases - physiology
Deoxyribonucleic acid
DNA
Experiments
Gene expression
Genome, Viral
Genomes
Genomics
HeLa Cells
Humans
Immunity, Innate
Immunoglobulin G - immunology
Infections
Influence
Medical research
Mice
Mice, Inbred C57BL
Nucleotidyltransferases - physiology
Pathogens
Pattern recognition
Phagocytosis
Picornaviridae Infections - immunology
Receptors, Immunologic
Rhinovirus
Ribonucleoproteins - physiology
Sensors
Software
Viral infections
Virus Diseases - immunology
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1005253