Publication Date:
2015-10-24
Description:
The nucleotide-binding oligomerization domain-like receptor (Nlrp) 6 maintains gut microbiota homeostasis and regulates antibacterial immunity. We now report a role for Nlrp6 in the control of enteric virus infection. Nlrp6(-/-) and control mice systemically challenged with encephalomyocarditis virus had similar mortality; however, the gastrointestinal tract of Nlrp6(-/-) mice exhibited increased viral loads. Nlrp6(-/-) mice orally infected with encephalomyocarditis virus had increased mortality and viremia compared with controls. Similar results were observed with murine norovirus 1. Nlrp6 bound viral RNA via the RNA helicase Dhx15 and interacted with mitochondrial antiviral signaling protein to induce type I/III interferons (IFNs) and IFN-stimulated genes (ISGs). These data demonstrate that Nlrp6 functions with Dhx15 as a viral RNA sensor to induce ISGs, and this effect is especially important in the intestinal tract.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Penghua -- Zhu, Shu -- Yang, Long -- Cui, Shuang -- Pan, Wen -- Jackson, Ruaidhri -- Zheng, Yunjiang -- Rongvaux, Anthony -- Sun, Qiangming -- Yang, Guang -- Gao, Shandian -- Lin, Rongtuan -- You, Fuping -- Flavell, Richard -- Fikrig, Erol -- AI099625/AI/NIAID NIH HHS/ -- AI103807/AI/NIAID NIH HHS/ -- N01-HHSN272201100019C/PHS HHS/ -- R03 AI099625/AI/NIAID NIH HHS/ -- R21 AI103807/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):826-30. doi: 10.1126/science.aab3145. Epub 2015 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA. ; Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. ; Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. ; Department of Genetics, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. ; Lady Davis Institute, Department of Medicine, McGill University, Montreal, Quebec, Canada. ; Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA. richard.flavell@yale.edu erol.fikrig@yale.edu. ; Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA. richard.flavell@yale.edu erol.fikrig@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26494172" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Caliciviridae Infections/immunology/virology
;
Cardiovirus Infections/immunology/virology
;
Cytokines/genetics
;
Encephalomyocarditis virus/immunology
;
Gastroenteritis/immunology/virology
;
Gene Expression Regulation
;
HEK293 Cells
;
Humans
;
Immunity, Innate/*genetics
;
Interferon Type I/*immunology
;
Intestines/*immunology/*virology
;
Mice
;
Mice, Mutant Strains
;
Norovirus/immunology
;
RNA Helicases/*physiology
;
RNA, Viral/*immunology
;
Receptors, Cell Surface/genetics/*physiology
;
Ubiquitins/genetics
;
Viremia/genetics/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
