Specific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular viral replication is recognized by a family of cytosolic RNA helicases termed RIG-I-like receptors (RLRs). The RLR proteins include RIG-I, MDA5, and LGP2 and are expressed in both immune and nonimmune cells. Upon recognition of viral nucleic acids, RLRs recruit specific intracellular adaptor proteins to initiate signaling pathways that lead to the synthesis of type I interferon and other inflammatory cytokines, which are important for eliminating viruses.

Organismal Systems; Immune system
BRITE hierarchy

nt06133  RLR signaling (viruses)
nt06162  Hepatitis B virus (HBV)
nt06163  Hepatitis C virus (HCV)
nt06165  Epstein-Barr virus (EBV)
nt06168  Herpes simplex virus 1 (HSV-1)
nt06169  Measles virus (MV)
nt06170  Influenza A virus (IAV)
nt06171  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
nt06263  Hepatocellular carcinoma

Homo sapiens (human) [GN:hsa]

PMID:15208624

Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T

The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.

Nat Immunol 5:730-7 (2004)
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PMID:18272355

Takeuchi O, Akira S

MDA5/RIG-I and virus recognition.

Curr Opin Immunol 20:17-22 (2008)
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PMID:19120475

Yoneyama M, Fujita T

RNA recognition and signal transduction by RIG-I-like receptors.

Immunol Rev 227:54-65 (2009)
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PMID:19539500

Nakhaei P, Genin P, Civas A, Hiscott J

RIG-I-like receptors: sensing and responding to RNA virus infection.

Semin Immunol 21:215-22 (2009)
DOI:10.1016/j.smim.2009.05.001

PMID:18549796

Moore CB, Ting JP

Regulation of mitochondrial antiviral signaling pathways.

Immunity 28:735-9 (2008)
DOI:10.1016/j.immuni.2008.05.005

PMID:19615405

Barral PM, Sarkar D, Su ZZ, Barber GN, DeSalle R, Racaniello VR, Fisher PB

Functions of the cytoplasmic RNA sensors RIG-I and MDA-5: key regulators of innate immunity.

Pharmacol Ther 124:219-34 (2009)
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PMID:19120476

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Approaching the RNA ligand for RIG-I?

Immunol Rev 227:66-74 (2009)
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PMID:18591413

Saito T, Gale M Jr

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J Exp Med 205:1523-7 (2008)
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PMID:19076341

Kawai T, Akira S

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Ann N Y Acad Sci 1143:1-20 (2008)
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PMID:18439848

Michallet MC, Meylan E, Ermolaeva MA, Vazquez J, Rebsamen M, Curran J, Poeck H, Bscheider M, Hartmann G, Konig M, Kalinke U, Pasparakis M, Tschopp J

TRADD protein is an essential component of the RIG-like helicase antiviral pathway.

Immunity 28:651-61 (2008)
DOI:10.1016/j.immuni.2008.03.013

PMID:18984593

Yoshida R, Takaesu G, Yoshida H, Okamoto F, Yoshioka T, Choi Y, Akira S, Kawai T, Yoshimura A, Kobayashi T

TRAF6 and MEKK1 play a pivotal role in the RIG-I-like helicase antiviral pathway.

J Biol Chem 283:36211-20 (2008)
DOI:10.1074/jbc.M806576200

PMID:19224920

Mikkelsen SS, Jensen SB, Chiliveru S, Melchjorsen J, Julkunen I, Gaestel M, Arthur JS, Flavell RA, Ghosh S, Paludan SR

RIG-I-mediated activation of p38 MAPK is essential for viral induction of interferon and activation of dendritic cells: dependence on TRAF2 and TAK1.

J Biol Chem 284:10774-82 (2009)
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