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Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity
- Source :
- PLoS ONE, Vol 7, Iss 8, p e43031 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) function as cytoplasmic sensors for viral RNA to initiate antiviral responses including type I interferon (IFN) production. It has been unclear how RIG-I encounters and senses viral RNA. To address this issue, we examined intracellular localization of RIG-I in response to viral infection using newly generated anti-RIG-I antibody. Immunohistochemical analysis revealed that RLRs localized in virus-induced granules containing stress granule (SG) markers together with viral RNA and antiviral proteins. Because of similarity in morphology and components, we termed these aggregates antiviral stress granules (avSGs). Influenza A virus (IAV) deficient in non-structural protein 1 (NS1) efficiently generated avSGs as well as IFN, however IAV encoding NS1 produced little. Inhibition of avSGs formation by removal of either the SG component or double-stranded RNA (dsRNA)-dependent protein kinase (PKR) resulted in diminished IFN production and concomitant enhancement of viral replication. Furthermore, we observed that transfection of dsRNA resulted in IFN production in an avSGs-dependent manner. These results strongly suggest that the avSG is the locus for non-self RNA sensing and the orchestration of multiple proteins is critical in the triggering of antiviral responses.
- Subjects :
- Viral Diseases
viruses
lcsh:Medicine
Antibodies, Viral
Biochemistry
DEAD-box RNA Helicases
Mice
eIF-2 Kinase
Interferon
Chlorocebus aethiops
Molecular Cell Biology
lcsh:Science
Immune Response
Cellular Stress Responses
Mice, Knockout
Multidisciplinary
RIG-I
Immunohistochemistry
Innate Immunity
RNA silencing
Infectious Diseases
Influenza A virus
Interferon Type I
Cytochemistry
DEAD Box Protein 58
RNA, Viral
Medicine
Immunohistochemical Analysis
Immunocytochemistry
Research Article
medicine.drug
Immunology
Biology
Cytoplasmic Granules
Immune Activation
Stress granule
Orthomyxoviridae Infections
medicine
Animals
Humans
Immunoassays
Vero Cells
lcsh:R
Immunity
RNA
Immune Defense
Fibroblasts
Virology
Protein kinase R
Immunity, Innate
Influenza
Viral replication
Immunologic Techniques
lcsh:Q
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....1a2e473c1f4dae55d40f908dc05dbc2a