Interleukin 28B

Interferon, lambda 3
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3HHC
Identifiers
Symbols	IFNL3 ; IL-28B; IL28B; IL28C
External IDs	OMIM: 607402 HomoloGene: 77540 GeneCards: IFNL3 Gene
Gene ontology Molecular function • receptor binding • cytokine activity Cellular component • extracellular space • intracellular Biological process • JAK-STAT cascade • negative regulation of viral genome replication • innate immune response • positive regulation of immune response • regulation of T cell activation • defense response to virus • positive regulation of protein targeting to mitochondrion Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	282617	330496
Ensembl	ENSG00000197110	ENSMUSG00000059128
UniProt	Q8IZI9	Q4VK74
RefSeq (mRNA)	NM_172139	NM_001024673
RefSeq (protein)	NP_742151	NP_001019844
Location (UCSC)	Chr 19: 39.24 – 39.25 Mb	Chr 7: 28.51 – 28.51 Mb
PubMed search

Interleukin 28B (interferon-λ 3) is a protein that in humans is encoded by the IL28B gene. IL28B has recently been renamed IFNL3 as its official gene symbol.^[1]

This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 29 (IL29) are three closely related cytokine genes that form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by the three genes can be induced by viral infection. All three cytokines have been shown to interact with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA). [provided by RefSeq, Jul 2008].^[1]

Implications to hepatitis C treatment

In individuals with chronic hepatitis C, the presence of specific polymorphisms near the IL28B gene has been associated with an increased response in treatment for the condition with interferon and ribavirin.^[2] The same polymorphisms were also demonstrated at higher frequencies in individuals infected with hepatitis C who cleared the infection spontaneously, compared to those that developed chronic hepatitis from the condition.^[3][4] A functional variant that determines the production of an antiviral protein has been linked to the polymorphisms in IL28B and implicated in the clearance of hepatitis C virus.^[5]

A non-coding genetic polymorphism (rs4803217) has been shown to significantly change the RNA structure and translation of IFNL3. The dynamic structure of the non-coding RNA produced by the rs4803217 polymorphism may be responsible for the increased HCV clearance of this allele.^[6]

References

1. "Entrez Gene: Interleukin 28B (interferon, lambda 3)". Retrieved 2012-01-27.
2. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (Sep 2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature 461 (7262): 399–401. doi:10.1038/nature08309. PMID 19684573.
3. Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O'Huigin C, Kidd J, Kidd K, Khakoo SI, Alexander G, Goedert JJ, Kirk GD, Donfield SM, Rosen HR, Tobler LH, Busch MP, McHutchison JG, Goldstein DB, Carrington M (Oct 2009). "Genetic variation in IL28B and spontaneous clearance of hepatitis C virus". Nature 461 (7265): 798–801. doi:10.1038/nature08463. PMC 3172006. PMID 19759533.
4. Muir AJ, Gong L, Johnson SG, Lee MT, Williams MS, Klein TE, Caudle KE, Nelson DR (Feb 2014). "Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-α-based regimens". Clinical Pharmacology and Therapeutics 95 (2): 141–6. doi:10.1038/clpt.2013.203. PMC 3904555. PMID 24096968.
5. Lu YF, Goldstein DB, Urban TJ, Bradrick SS (Feb 2015). "Interferon-λ4 is a cell-autonomous type III interferon associated with pre-treatment hepatitis C virus burden". Virology 476: 334–40. doi:10.1016/j.virol.2014.12.020. PMID 25577150.
6. Lu YF, Mauger DM, Goldstein DB, Urban TJ, Weeks KM, Bradrick SS (Nov 2015). "IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance". Scientific Reports 5: 16037. doi:10.1038/srep16037. PMID 26531896.

Further reading

• Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM (Jan 2003). "IL-28, IL-29 and their class II cytokine receptor IL-28R". Nature Immunology 4 (1): 63–68. doi:10.1038/ni873. PMID 12469119.
• Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP (Jan 2003). "IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex". Nature Immunology 4 (1): 69–77. doi:10.1038/ni875. PMID 12483210.
• Li M, He S (Apr 2006). "Purification and characterization of recombinant human interleukin-29 expressed in Escherichia coli". Journal of Biotechnology 122 (3): 334–340. doi:10.1016/j.jbiotec.2005.11.019. PMID 16413080.
• Mennechet FJ, Uzé G (Jun 2006). "Interferon-lambda-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells". Blood 107 (11): 4417–4423. doi:10.1182/blood-2005-10-4129. PMID 16478884.
• Li MC, Wang HY, Wang HY, Li T, He SH (Apr 2006). "Liposome-mediated IL-28 and IL-29 expression in A549 cells and anti-viral effect of IL-28 and IL-29 on WISH cells". Acta Pharmacologica Sinica 27 (4): 453–459. doi:10.1111/j.1745-7254.2006.00292.x. PMID 16539846.
• Lasfar A, Lewis-Antes A, Smirnov SV, Anantha S, Abushahba W, Tian B, Reuhl K, Dickensheets H, Sheikh F, Donnelly RP, Raveche E, Kotenko SV (Apr 2006). "Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma". Cancer Research 66 (8): 4468–4477. doi:10.1158/0008-5472.CAN-05-3653. PMID 16618774.
• Dellgren C, Gad HH, Hamming OJ, Melchjorsen J, Hartmann R (Mar 2009). "Human interferon-lambda3 is a potent member of the type III interferon family". Genes and Immunity 10 (2): 125–131. doi:10.1038/gene.2008.87. PMID 18987645.
• Li M, Liu X, Zhou Y, Su SB (Jul 2009). "Interferon-lambdas: the modulators of antivirus, antitumor, and immune responses". Journal of Leukocyte Biology 86 (1): 23–32. doi:10.1189/jlb.1208761. PMID 19304895.
• Gad HH, Dellgren C, Hamming OJ, Vends S, Paludan SR, Hartmann R (Jul 2009). "Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family". The Journal of Biological Chemistry 284 (31): 20869–20875. doi:10.1074/jbc.M109.002923. PMC 2742852. PMID 19457860.
• Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (Sep 2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature 461 (7262): 399–401. doi:10.1038/nature08309. PMID 19684573.