{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T14:11:13Z","timestamp":1772806273998,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,19]],"date-time":"2008-12-19T00:00:00Z","timestamp":1229644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:p><jats:bold>Summary:\u2002<\/jats:bold> Innate and antigen\u2010specific antiviral immunity are triggered by immunorecognition of viral nucleic acids. The helicase retinoic acid\u2010inducible gene I (RIG\u2010I) (also known as DDX58) is the key sensor of negative strand RNA viruses in the cytosol of cells. RNA containing a triphosphate at the 5\u2032\u2010end was shown to activate RIG\u2010I, but the exact structure of RNA supporting 5\u2032\u2010triphosphate recognition, the requirement of a 5\u2032\u2010triphosphate group, as well as the existence of RNA structures detected by RIG\u2010I in the absence of 5\u2032\u2010triphosphate remain controversial. Here, we revisit the literature on RIG\u2010I and RIG\u2010I ligands. The literature proposes at least six different RIG\u2010I ligands: (i) single strand with a 5\u2032\u2010triphosphate, (ii) double\u2010stranded RNA with a 5\u2032\u2010triphosphate, (iii) 5\u2032\u2010triphosphate single\u2010stranded RNA with A\u2010 and U\u2010rich 3\u2032\u2010sequences, (iv) double\u2010stranded RNA of intermediate length (&gt;300 and &lt;2000\u2003bp) without 5\u2032\u2010triphosphate, (v) blunt\u2010end short double\u2010stranded RNA (23\u201330\u2003bp) without 5\u2032\u2010triphosphate, and (vi) short double\u2010stranded RNA (23\u201330\u2003bp) with 5\u2032\u2010monophosphate. RIG\u2010I thus seems promiscuous for a variety of different RNA molecules, very similar to the Toll\u2010like receptors, of which 10 family members are sufficient for the safe detection of the microbial cosmos. In the light of these outstanding publications, it seems an unlikely possibility that there is a fundamental shortcoming in the design of all studies. Looking closely, the only issue that comes to mind is the <jats:italic>in vitro<\/jats:italic> transcription technique used by all investigators without confirming the identity of RNA products. This technique, together with the different biological systems used, the lack of dose responses and of proper comparison of different published ligands and controls leave us with more questions than answers as to what the exact RIG\u2010I ligand is, if in fact it exists.<\/jats:p>","DOI":"10.1111\/j.1600-065x.2008.00724.x","type":"journal-article","created":{"date-parts":[[2008,12,25]],"date-time":"2008-12-25T02:47:01Z","timestamp":1230173221000},"page":"66-74","source":"Crossref","is-referenced-by-count":65,"title":["Approaching the RNA ligand for 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