Publication Date:
2006-10-14
Description:
The structural basis for the distinction of viral RNA from abundant self RNA in the cytoplasm of virally infected cells is largely unknown. We demonstrated that the 5'-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid-inducible protein I (RIG-I)-mediated detection of RNA molecules. Detection of 5'-triphosphate RNA is abrogated by capping of the 5'-triphosphate end or by nucleoside modification of RNA, both occurring during posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a negative-strand RNA virus and RNA prepared from virus-infected cells (but not from noninfected cells) triggered a potent interferon-alpha response in a phosphatase-sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. Thus, uncapped 5'-triphosphate RNA (now termed 3pRNA) present in viruses known to be recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as the picornaviruses, serves as the molecular signature for the detection of viral infection by RIG-I.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hornung, Veit -- Ellegast, Jana -- Kim, Sarah -- Brzozka, Krzysztof -- Jung, Andreas -- Kato, Hiroki -- Poeck, Hendrik -- Akira, Shizuo -- Conzelmann, Karl-Klaus -- Schlee, Martin -- Endres, Stefan -- Hartmann, Gunther -- New York, N.Y. -- Science. 2006 Nov 10;314(5801):994-7. Epub 2006 Oct 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17038590" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Line
;
Cells, Cultured
;
Cytosol/metabolism/virology
;
DEAD-box RNA Helicases/*metabolism
;
DNA-Directed RNA Polymerases/metabolism
;
Humans
;
Interferon-alpha/biosynthesis
;
Interferon-beta/biosynthesis
;
Ligands
;
Mice
;
Monocytes/metabolism
;
Oligoribonucleotides/metabolism
;
Phosphates/metabolism
;
Phosphorylation
;
RNA/chemistry/*metabolism
;
RNA Caps/metabolism
;
RNA, Double-Stranded/chemistry/metabolism
;
RNA, Viral/chemistry/*metabolism
;
Rabies virus/genetics/immunology/physiology
;
Transcription, Genetic
;
Transfection
;
Viral Proteins/metabolism
;
Virus Replication
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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