Central roles of NLRs and inflammasomes in viral infection
- 17 September 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Immunology
- Vol. 10 (10), 688-698
- https://doi.org/10.1038/nri2851
Abstract
Inflammasomes and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) mediate the recognition of viruses by detecting evolutionarily conserved motifs in their genomic RNA or DNA. In addition to viral RNA, NLR family PYD-containing protein 3 (NLRP3) senses a large number of pathogen-associated molecular patterns (PAMPs) through incompletely characterized mechanisms, such as ion flux that is caused by viral ion channels or multiple coordinated signals. Inflammasomes have a crucial role in the immune response to viral infections. NLR proteins were previously thought to be the only mediators of inflammasome activation. However, recent research has shown that members of additional cytoplasmic pattern-recognition receptor (PRR) families, such as retinoic acid inducible gene-I (RIG-I) and absent in melanoma 2 (AIM2), can activate the inflammasome in virus-infected cells. NOD2, which was originally reported to activate mitogen-activated protein kinase and nuclear factor-κB signalling through receptor-interacting serine-threonine protein kinase 2 (RIPK2), in response to bacterial peptidoglycan, has been shown to also signal through mitochondrial antiviral signalling protein (MAVS) and to induce the production of type I interferons (IFNs) in response to viral single-stranded RNA. NLR proteins also have regulatory functions during virus infection. NLRX1 negatively regulates type I IFN production that is mediated by the RIG-I–MAVS–IFN response factor 3 (IRF3) signalling cascade. Crosstalk between innate immune signalling pathways has become increasingly evident. RIG-I was originally discovered as a mediator of type I IFN production but is now recognized as a potential inflammasome activator also. Several viruses encode inhibitors of inflammasome and MAVS signalling pathways, thereby indicating an important role for these pathways in controlling virus replication and the requirement for viruses to interfere with their activation to successfully infect a host.Keywords
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