Interferon type III[edit]

Interferon type III (λ)

Identifiers

Symbol

IFN-λ 1–3

Pfam

PF15177

InterPro

IPR029177

CATH

3og6A00

showAvailable protein structures:

The type III interferon group consists of four IFN-λ (lambda) molecules called IFN-λ1, IFN-λ2, IFN-λ3 (formerly IL29, IL28A and IL28B respectively), and IFN-λ4.^[1] These interferons signal through a receptor complex consisting of IL10RB (also called IL10R2 or CRF2-4) and IFNLR1 (formerly called IL28RA , CRF2-12).^[2] The interferon lambda genes lie in the 19q13.13 chromosomal region. IFNL4 is located between IFNL3 and IFNL2.^[3]

Interferon lambda proteins are involved in immune response to viral infection. Signaling initiated by IFN-λ triggers the JAK-STAT pathway, leading to the expression of numerous interferon-stimulated genes with anti-viral and anti-proliferative effects.

All four interferon lambda proteins have antiviral effects in vitro, however, a genetic variant that produces the IFNL4 protein is linked to impaired clearance of hepatitis C virus.^[3] The explanation for this paradox is not fully understood.

In contrast to the ubiquitous expression of receptors for IFN-α, IFNLR1 is largely restricted to tissues of epithelial origin.^[4]^[5] Therefore, interferon lambda proteins may have evolved specifically to protect tissue barriers.

^ Vilcek, Jan (2003). "Novel interferons". Nature Immunology. 4 (1): 8–9. doi:10.1038/ni0103-8. ISSN 1529-2908. PMID 12496969.
^ Bartlett, Nathan W.; Buttigieg, Karen; Kotenko, Sergei V.; Smith, Geoffrey L. (2005). "Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model". The Journal of General Virology. 86 (Pt 6): 1589–1596. doi:10.1099/vir.0.80904-0. ISSN 0022-1317. PMID 15914836.
^ ^a ^b Prokunina-Olsson, Ludmila; Muchmore, Brian; Tang, Wei; Pfeiffer, Ruth M.; Park, Heiyoung; Dickensheets, Harold; Hergott, Dianna; Porter-Gill, Patricia; Mumy, Adam; Kohaar, Indu; Chen, Sabrina (2013). "A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus". Nature Genetics. 45 (2): 164–171. doi:10.1038/ng.2521. ISSN 1546-1718. PMC 3793390. PMID 23291588.
^ Kotenko, Sergei V.; Gallagher, Grant; Baurin, Vitaliy V.; Lewis-Antes, Anita; Shen, Meiling; Shah, Nital K.; Langer, Jerome A.; Sheikh, Faruk; Dickensheets, Harold; Donnelly, Raymond P. (2003). "IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex". Nature Immunology. 4 (1): 69–77. doi:10.1038/ni875. ISSN 1529-2908. PMID 12483210.
^ Sheppard, Paul; Kindsvogel, Wayne; Xu, Wenfeng; Henderson, Katherine; Schlutsmeyer, Stacy; Whitmore, Theodore E.; Kuestner, Rolf; Garrigues, Ursula; Birks, Carl; Roraback, Jenny; Ostrander, Craig (2003). "IL-28, IL-29 and their class II cytokine receptor IL-28R". Nature Immunology. 4 (1): 63–68. doi:10.1038/ni873. ISSN 1529-2908. PMID 12469119.

[1] Vilcek, Jan (2003). "Novel interferons". Nature Immunology. 4 (1): 8–9. doi:10.1038/ni0103-8. ISSN 1529-2908. PMID 12496969.

[2] Bartlett, Nathan W.; Buttigieg, Karen; Kotenko, Sergei V.; Smith, Geoffrey L. (2005). "Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model". The Journal of General Virology. 86 (Pt 6): 1589–1596. doi:10.1099/vir.0.80904-0. ISSN 0022-1317. PMID 15914836.

[:0-3] Prokunina-Olsson, Ludmila; Muchmore, Brian; Tang, Wei; Pfeiffer, Ruth M.; Park, Heiyoung; Dickensheets, Harold; Hergott, Dianna; Porter-Gill, Patricia; Mumy, Adam; Kohaar, Indu; Chen, Sabrina (2013). "A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus". Nature Genetics. 45 (2): 164–171. doi:10.1038/ng.2521. ISSN 1546-1718. PMC 3793390. PMID 23291588.

[4] Kotenko, Sergei V.; Gallagher, Grant; Baurin, Vitaliy V.; Lewis-Antes, Anita; Shen, Meiling; Shah, Nital K.; Langer, Jerome A.; Sheikh, Faruk; Dickensheets, Harold; Donnelly, Raymond P. (2003). "IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex". Nature Immunology. 4 (1): 69–77. doi:10.1038/ni875. ISSN 1529-2908. PMID 12483210.

[5] Sheppard, Paul; Kindsvogel, Wayne; Xu, Wenfeng; Henderson, Katherine; Schlutsmeyer, Stacy; Whitmore, Theodore E.; Kuestner, Rolf; Garrigues, Ursula; Birks, Carl; Roraback, Jenny; Ostrander, Craig (2003). "IL-28, IL-29 and their class II cytokine receptor IL-28R". Nature Immunology. 4 (1): 63–68. doi:10.1038/ni873. ISSN 1529-2908. PMID 12469119.

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