WordNet

first in order of importance; "the alpha male in the group of chimpanzees"; "the alpha star in a constellation is the brightest or main star"
the 1st letter of the Greek alphabet
the beginning of a series or sequence; "the Alpha and Omega, the first and the last, the beginning and the end"--Revelations
early testing stage of a software or hardware product; "alpha version"
an antiviral protein produced by cells that have been invaded by a virus; inhibits replication of the virus
any high mountain

PrepTutorEJDIC

アルファ(ギリシア語アルファベットの第1字A,α;英語のA,aに相当) / アルファ星(星座の主星)
インターフェロン(ウイルス増殖抑制物質)
高山,高峰
インターフェロン (virusの増殖を抑制する)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/08 09:37:44」(JST)

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The 3D structure of human IFN-β

Human type I interferons comprise a vast and growing group of IFN proteins.

All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains.

Homologous molecules to type I IFNs are found in many species, including all mammals, and some have been identified in birds, reptiles, amphibians and fish species.^[1]

Mammalian types

The mammalian types are designated IFN-α (alpha), IFN-β (beta), IFN-κ (kappa), IFN-δ (delta), IFN-ε (epsilon), IFN-τ (tau), IFN-ω (omega), and IFN-ζ (zeta, also known as limitin).^[2]^[3]

IFN-α

The IFN-α proteins are produced by leukocytes. They are mainly involved in innate immune response against viral infection. They come in 13 subtypes that are called IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21. These genes for these IFN-α molecules are found together in a cluster on chromosome 9.

IFN-α is also made synthetically as medication. Types are:

Pegylated interferon alfa-2a
Pegylated interferon alfa-2b

IFN-β

The IFN-β proteins are produced in large quantities by fibroblasts. They have antiviral activity which is mainly involved in innate immune response. Two types of IFN-β have been described, IFN-β1 (IFNB1) and IFN-β3 (IFNB3)^[4] (a gene designated IFN-β2 is actually IL-6). IFN-β1 is used as a treatment for multiple sclerosis as it reduces the relapse rate.

IFN-ε, –κ, -τ, -δ, and –ζ

IFN-ε, –κ, -τ, and –ζ appear, at this time, to come in a single isoform in humans, IFNK. Only ruminants encode IFN-τ, a variant of IFN-ω. So far, IFN-ζ is found only in mice, while a structural homolog, IFN-δ is found in a diverse array of non-primate and non-rodent placental mammals. Most but not all placental mammals encode functional IFN-ε and IFN-κ genes.

IFN-ω

IFN-ω, although having only one functional form described to date (IFNW1), has several pseudogenes: IFNWP2, IFNWP4, IFNWP5, IFNWP9, IFNWP15, IFNWP18, and IFNWP19 in humans. Many non-primate placental mammals express multiple IFN-ω subtypes

IFN-ν

This subtype of Type I IFN was recently described as a pseudogene in human, but potentially functional in the domestic cat genome. In all other genomes of non-feline placental mammals, IFN-ν is a pseudogene; in some species, the pseudogene is well preserved, while in others, it is badly mutilated or is undetectable. Moreover, in the cat genome, the IFN-ν promoter is deleteriously mutated. It is likely that the IFN-ν gene family was rendered useless prior to mammalian diversification. Its presence on the edge of the Type I IFN locus in mammals may have shielded it from obliteration, allowing its detection.

Sources and functions

IFN-α and IFN-β are secreted by many cell types including lymphocytes (NK cells, B-cells and T-cells), macrophages, fibroblasts, endothelial cells, osteoblasts and others. They stimulate both macrophages and NK cells to elicit an anti-viral response, and are also active against tumors. Recently, plasmacytoid dendritic cells have been identified as being the most potent producers of type I IFNs in response to antigen, and have thus been coined natural IFN producing cells.

IFN-ω is released by leukocytes at the site of viral infection or tumors.

IFN-α acts as a pyrogenic factor by altering the activity of thermosensitive neurons in the hypothalamus thus causing fever. It does this by binding to opioid receptors and eliciting the release of prostaglandin-E₂ (PGE₂).

A similar mechanism is used by IFN-α to reduce pain; IFN-α interacts with the μ-opioid receptor to act as an analgesic.^[5]

Non-mammalian types

Avian Type I IFNs have been characterized and preliminarily assigned to subtypes (IFN I, IFN II, and IFN III), but their classification into subtypes should await a more extensive characterization of avian genomes.

Functional lizard Type I IFNs can be found in lizard genome databases.

Turtle Type I IFNs have been purified (references from 1970s needed). They resemble mammalian homologs.

The existence of amphibian Type I IFNs have been inferred by the discovery of the genes encoding their receptor chains. They have not yet been purified, or their genes cloned.

Piscine (bony fish) Type I IFN has been cloned in several teleost species. With few exceptions, and in stark contrast to avian and especially mammalian IFNs, they are present as single genes (multiple genes are however seen in polyploid fish genomes, possibly arising from whole-genome duplication). Unlike amniote IFN genes, piscine Type I IFN genes contain introns, in similar positions as do their orthologs, certain interleukins.

References

^ Schultz et al., The interferon system of non-mammalian vertebrates. Developmental and Comparative Immunology, Volume 28, pages 499-508.
^ Oritani and Tomiyama, Interferon-ζ/limitin: Novel type I Interferon that displays a narrow range of biological activity. International journal of hematology, 2004, Volume 80, pages 325-331 .
^ Hardy et al., Characterization of the type I interferon locus and identification of novel genes. Genomics, 2004, Volume 84 pages 331-345.
^ Todd and Naylor, New chromosomal mapping assignments for argininosuccinate synthetase pseudogene 1, interferon-beta 3 gene, and the diazepam binding inhibitor gene. Somat. Cell. Mol. Genet. 1992 Volume 18, pages 381-5.
^ Wang et al., Fever of recombinant human interferon-alpha is mediated by opioid domain interaction with opioid receptor inducing prostaglandin E2. J Neuroimmunol. 2004 Nov;156(1-2):107-12.

External links

Interferon+Type+I at the US National Library of Medicine Medical Subject Headings (MeSH)

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English Journal

Nucleoside/Nucleotide analogue polymerase inhibitors in development.

Pockros PJ.SourceDivision of Gastroenterology/Hepatology, Liver Disease Center, Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, CA 92067, USA. Electronic address: pockros.paul@scrippshealth.org.
Clinics in liver disease.Clin Liver Dis.2013 Feb;17(1):105-10. doi: 10.1016/j.cld.2012.09.007.
Nucleoside/nucleotide analogue polymerase inhibitors (NPIs) are analogues of natural substrates that bind the active site of NS5B and terminate viral RNA chain generation and generally provide a high genetic barrier to resistance and are effective in all genotypes. NPIs such as sofosbuvir (GS-7977)
PMID 23177286

NF-κB1 deficiency stimulates the progression of non-alcoholic steatohepatitis (NASH) in mice by promoting NKT-cell-mediated responses.

Locatelli I, Sutti S, Vacchiano M, Bozzola C, Albano E.SourceDepartment of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University 'Amedeo Avogadro' of East Piedmont, Via Solaroli 17, 28100 Novara, Italy.
Clinical science (London, England : 1979).Clin Sci (Lond).2013 Feb 1;124(4):279-87. doi: 10.1042/CS20120289.
Growing evidence indicates that NF-κB (nuclear factor κB) activation contributes to the pathogenesis of NASH (non-alcoholic steatohepatisis). Among the NF-κB subunits, p50/NF-κB1 has regulatory activities down-modulating NF-κB-mediated responses. In the present study, we investigated the effect
PMID 22970906

Japanese Journal

腎癌心膜転移による心タンポナーデをきたした1例

上田倫央,新井康之,松崎恭介 [他]
泌尿器科紀要 58(9), 491-494, 2012-09
… After 7 years, he was diagnosed with mediastinal lymph node metastasis and we performed interferon-alpha therapy. …
NAID 40019429517