TABLE 1.

TLR and RLR ligands

Sensors	Ligand characteristics	Synthetic RNA	Microbial RNA	Host RNA	Key references
TLR3	dsRNA	dsRNA ≥ 39–48 bpds dsRNA ≥ 90 bp (intracellular TLR3 only) siRNA	Viral and bacterial RNA (e.g. long stem-loop containing poliovirus- derived RNA)	Phagocytosed host RNA (context-dependent)	(Kariko et al., 2004a; Kariko et al., 2004b; Kleinman et al., 2008; Leonard et al., 2008; Liu et al., 2008; Tatematsu et al., 2013)
TLR7	Site 1: guanosine	UU(U/C) > UU(G/A) > XUX (X = non-U) siRNA	Viral and bacterial RNA (e.g. HIV GU-rich RNA)	Let-7 miRNA	(Heil et al., 2004; Hornung et al., 2005; Lehmann et al., 2012; Tanji et al., 2015; Zhang et al., 2016; Zhang et al., 2018b)
	Site 2: ssRNA
TLR8	Site 1: uridine	UG dinucleotide	Viral and bacterial RNA	N/A
	Site 2: ssRNA
TLR13	Stem-loop ssRNA	≥ 13 nt	Bacterial 23S rRNA VSV ssRNA genome	N/A	(Li and Chen, 2012; Oldenburg et al., 2012; Song et al., 2015)
RIG-I	5’-di- or triphosphate and blunt-ended dsRNA	Short dsRNA of ≥ 10–19 bp	Sub(genomic) RNA of negative-strand RNA viruses (e.g. IAV panhandle structure) Reovirus and yeast L-A totivirus genomic RNA	N/A	(Baum et al., 2010; Goubau et al., 2014; Hornung et al., 2006; Liu et al., 2015; Pichlmair et al., 2006; Schlee et al., 2009; Schmidt et al., 2009)
	‘Non-canonical’	RNase Ill-digested poly(I:C) of ≤ 300 bp Pol III transcripts of poly(dA-dT)	HCV 3’ UTR Measles virus L gene mRNA; KSHV RNA transcripts EBV-encoded small RNAs (EBERs); adenovirus-associated RNA (VA-RNAs)	5S ribosomal RNA pseudogene 141 Vault RNA lnc-Lsm3b RNase L cleavage products; IRE-1 cleavage products Circular RNA	(Ablasser et al., 2009; Chen et al., 2017; Chiang et al., 2018; Chiu et al., 2009; Eckard et al., 2014; Jiang et al., 2018; Kato et al., 2008; Malathi et al., 2007; Minamitani et al., 2011; Runge et al., 2014; Saito et al., 2008; Zhang et al., 2018a; Zhao et al., 2018)
MDA5	Long irregular dsRNA	Poly(I:C) of > 300 bp	Parainfluenza virus 5 and measles virus L gene mRNA EMCV L antisense RNA	Inverted repeat transposable Alu elements (~300 bp) Mitochondrial dsRNA	(Ahmad et al., 2018; Deddouche et al., 2014; Dhir et al., 2018; Kato et al., 2008; Luthra et al., 2011; Pichlmair et al., 2009; Runge et al., 2014)
LGP2	dsRNA; no end specificity	dsRNA that is blunt-ended or has overhangs with or without 5’-triphosphate moiety	EMCV L antisense RNA	N/A	(Deddouche et al., 2014; Uchikawa et al., 2016)

Abbreviations: HIV, human immunodeficiency virus; VSV, vesicular stomatitis virus; IAV, influenza A virus; HCV, hepatitis C virus; KSHV, Kaposi’s sarcoma-associated herpesvirus; EBV, Epstein-Barr virus; IRE-1, inositol-requiring enzyme 1; EMCV, encephalomyocarditis virus; Alu, Arthrobacter luteus; N/A, not available.