IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex.
We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentatively designated as IL-29, IL-28A and IL-28B, respectively, by HUGO). The expression of IFN-lambda mRNAs was inducible by viral infection in several cell lines. We identified a distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) and a second subunit, CRF2-4 (also known as IL-10R2). Both receptor chains are constitutively expressed on a wide variety of human cell lines and tissues and signal through the Jak-STAT (Janus kinases-signal transducers and activators of transcription) pathway. This receptor-ligand system may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs.
Kotenko
Sergei V
SV
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. kotenkse@umdnj.edu
Gallagher
Grant
G
Baurin
Vitaliy V
VV
Lewis-Antes
Anita
A
Shen
Meiling
M
Shah
Nital K
NK
Langer
Jerome A
JA
Sheikh
Faruk
F
Dickensheets
Harold
H
Donnelly
Raymond P
RP
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D053710:Interleukin-10 Receptor beta Subunit; D008024:Ligands; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D018121:Receptors, Cytokine / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology
D000998:Antiviral Agents; D018076:DNA, Complementary; C081846:IL10RB protein, human; D053710:Interleukin-10 Receptor beta Subunit; D008024:Ligands; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D007372:Interferons