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Interferons (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. Interferons belong to the large class of glycoproteins known as cytokines. Interferons assist the immune response by inhibiting viral replication within other cells of the body. Image File history File links Broom_icon. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... This article does not cite any references or sources. ... This article is about biological infectious particles. ... Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ... A parasite is an organism that spends a significant portion of its life in or on the living tissue of a host organism and which causes harm to the host without immediately killing it. ... For malignant tumors specifically, see cancer. ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (a sugar). ... Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. ...

Types of interferon

There are three major classes of interferons that have been described for humans according to the type of receptor through which they signal:

• Interferon type I: 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.

• Interferon type II: Binds to IFNGR.

• Interferon type III: Signal through a receptor complex consisting of IL10R2 (also called CRF2-4) and IFNLR1 (also called CRF2-12)

The 3D structure of human IFN-β Human type I interferons comprise a vast and growing group of IFN proteins. ... IFNAR is a receptor which binds Interferon type I. MeSH Receptor,+Interferon+alpha-beta Categories: | | ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Interferon (alpha, beta and omega) receptor 2, also known as IFNAR2, is a human gene. ... The 3D structure of human IFN-γ A sole member makes up the type II IFNs that is called IFN-γ (gamma). ... IFNGR is a receptor which binds interferon-γ, the sole member of interferon type II. The human interferon-gamma receptor complex consists the heterodimer of two chains: IFNGR1 and IFNGR2[1][2]. In unstimulated cells, these subunits are not preassociated with each other but rather associate through their intracellular domains with... The recently classified type III interferon group consists of three IFN-λ (lambda) molecules called IFN-λ1, IFN-λ2 and IFN-λ3 (also called IL29, IL28A and IL28B respectively). ... Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Interleukin 28 receptor, alpha (interferon, lambda receptor), also known as IL28RA, is a human gene. ...

Signaling pathway

While there is evidence to suggest other signaling mechanisms exist, the JAK-STAT signaling pathway is the best-characterised and commonly accepted IFN signaling pathway. The JAK-STAT pathway (Janus Kinase - Signal Transduction Activating Transcription pathway) provides a secondary messenger facility (STAT) for polypeptide hormones, which are not fat soluble, to penetrate the cell membrane and deliver their message to the cell nucleus and DNA. In the field of interferon and cytokine signalling, the JAK...

Natural function and synthesis

Interferons in general have several effects in common. They are antiviral and possess antioncogenic properties, macrophage and natural killer lymphocyte activation, and enhancement of major histocompatibility complex glycoprotein classes I and II, and thus presentation of foreign (microbial) peptides to T cells. In a majority of cases, the production of interferons is induced in response to microbes such as viruses and bacteria and their products (viral glycoproteins, viral RNA, bacterial endotoxin, bacterial flagella, CpG sites), as well as mitogens and other cytokines, for example interleukin 1, interleukin 2, interleukin-12, tumor necrosis factor and colony-stimulating factor, that are synthesised in the response to the appearance of various antigens in the body. Their metabolism and excretion take place mainly in the liver and kidneys. They rarely pass the placenta but they can cross the blood-brain barrier. A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, from makros large + phagein eat) are cells within the tissues that originate from specific white blood cells called monocytes. ... Natural NK cells are cytotoxic; small granules in their cytoplasm contain special proteins such as perforin and proteases known as granzymes. ... Protein images comparing the MHC I (1hsa) and MHC II (1dlh) molecules. ... N-linked protein glycosylation (N-glycosylation of N-glycans) at Asn residues (Asn-x-Ser/Thr motifs) in glycoproteins[1]. Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbones. ... T cells are a subset of lymphocytes that play a large role in the immune response. ... CpG sites are regions of the DNA where a cytosine nucleotide is situated next to a guanine nucleotide. ... Interleukin-1 (IL-1) is secreted by the macrophages, monocytes and dendritic cells. ... Interleukin-2 (IL-2) is an interleukin, a type of biological response modifier, a substance that can improve the bodys natural response to disease. ... Interleukin 12 (IL-12) is an interleukin that are naturally produced by macrophages and human B-lymphoblastoid cells (NC-37)in response to antigenic stimulation. ... In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response. ... Colony-stimulating factor is a substance that stimulates the production of blood cells. ... The placenta is a sack of fat present in placental vertebrates, such as some mammals and sharks during gestation (pregnancy). ... The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ...

Viral induction of interferons

All classes of interferon are very important in fighting RNA virus infections. However, their presence also accounts for some of the host symptoms, such as sore muscles and fever. They are secreted when abnormally large amounts of dsRNA are found in a cell. dsRNA is normally present in very low quantities. The dsRNA acts like a trigger for the production of interferon (via Toll Like Receptor 3 (TLR 3) a pattern recognition receptor of the innate immune system which leads to activation of the transcription factor IRF3 and late phase NF kappa Beta). The gene that codes for this cytokine is switched on in an infected cell, and the interferon synthesized and secreted to surrounding cells. An RNA virus is a virus that either uses RNA as its genetic material, or whose genetic material passes through an RNA intermediate during replication. ... Left: An RNA strand, with its nitrogenous bases. ... TLR 3 is one of 11 Toll-like receptors part of the innate immune system. ... Pattern recognition receptors, or PRRs, are a class of cell surface receptors which are employed by the cells of the immune system to identify foreign (disease-associated) biomolecules in the body. ... IRF3 is an interferon regulatory factor. ...

As the original cell dies from the cytolytic RNA virus, these thousands of viruses will infect nearby cells. However, these cells have received interferon, which essentially warns these other cells that there's a wolf in the pack of sheep. They then start producing large amounts of a protein known as protein kinase R (or PKR). If a virus infects a cell that has been “pre-warned” by interferon, it is like charging into a hail of bullets for the virus. The PKR is indirectly activated by the dsRNA (actually by 2'-5' oligoadenylate produced by the 2'-5' oligoadenylate-synthetase which is produced due to TLR3 activation), and begins transferring phosphate groups (phosphorylating) to a protein known as eIF-2, a eukaryotic translation initiation factor. After phosphorylation, eIF2 has a reduced ability to initiate translation, the production of proteins coded by cellular mRNA. This prevents viral replication and inhibits normal cell ribosome function, killing both the virus and the host cell if the response is active for a sufficient amount of time. All RNA within the cell is also degraded, preventing the mRNA from being translated by eIF2 if some of the eIF2 failed to be phosphorylated. An RNA virus is a virus that either uses RNA as its genetic material, or whose genetic material passes through an RNA intermediate during replication. ... Protein kinase R (PKR) is activated by double-stranded RNA (dsRNA) and plays a major role in the cellular response to viral infection. ... Protein kinase R (PKR) is activated by double-stranded RNA (dsRNA) and plays a major role in the cellular response to viral infection. ... Left: An RNA strand, with its nitrogenous bases. ... A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein molecule or a small molecule. ... eIF-2 (Eukaryotic Initiation Factor 2) is a heterotrimer of subunits alpha, beta, and gamma. ... Kingdoms Eukaryotes are organisms with complex cells, in which the genetic material is organized into membrane-bound nuclei. ... The interaction of mRNA in a eukaryote cell. ... Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ...

Furthermore, interferon leads to upregulation of MHC I and therefore to increased presentation of viral peptides to cytotoxic CD8 T cells, as well as to a change in the proteasome (exchange of some beta subunits by b1i, b2i, b5i - then known as the immunoproteasome) which leads to increased production of MHC I compatible peptides.

Interferon can cause increased p53 activity in virus infected cells. It acts as an inducer and causes increased production of the p53 gene product. This promotes apoptosis, limiting the ability of the virus to spread. Increased levels of transcription are observed even in cells which are not infected, but only infected cells show increased apoptosis. This increased transcription may serve to prepare susceptible cells so they can respond quickly in the case of infection. When p53 is induced by viral presence, it behaves differently than it usually does. Some p53 target genes are expressed under viral load, but others, especially those that respond to DNA damage, aren’t. One of the genes that is not activated is p21, which can promote cell survival. Leaving this gene inactive would help promote the apoptotic effect. Interferon enhances the apoptotic effects of p53, but it is not strictly required. Normal cells exhibit a stronger apoptotic response than cells without p53.^[1][2] TP53 bound to a short DNA fragment. ... A section of mouse liver showing an apoptotic cell indicated by an arrow Apoptosis (pronounced apo tō sis) is a process of suicide by a cell in a multicellular organism. ...

Additionally, interferon has been shown to have therapeutic effect against certain cancers. It is probable that one mechanism of this effect is p53 induction. This could be useful clinically: Interferons could supplement or replace chemotherapy drugs that activate p53 but also cause unwanted side effects.^[1].Some of these side effects can be serious, severe and permanent. Chemotherapy is the use of chemical substances to treat disease. ...

Virus resistance to interferons

In a study of the blocking of interferon (IFN) by the Japanese Encephalitis Virus (JEV), a group of researchers infected human recombinant IFN-alpha with JEV, DEN-2, and PL406, which are all viruses, and found that some viruses have manifested methods that give them a way around the IFN-alpha/beta response. The viruses need to master these methods so they can have the ability to carry on viral replication and production of new viruses.^[3] The ways that viruses find a way around the IFN response is through the inhibition of interferon signaling, production, and the blocking of the functions of IFN-induced proteins.^[3]

It is not unusual to find viruses encoding for a multiple number of mechanisms to allow them to elude the IFN response at many different levels.^[3] While doing the study with JEV, Lin and his coworkers found that with IFN-alpha's inability to block JEV means that JEV may be able to block IFN-alpha signaling which in turn would prevent IFN from having STAT1, STAT2, ISGF3, and IRF-9 signaling.^[3] DEN-2 also significantly reduces interferon ability to active JAK-STAT.^[3]Some other viral gene products that have been found to have an effect on IFN signaling include EBNA-2, Polyomavirus large T antigen, EBV EBNA1, HPV E7, HCMV, and HHV8.^[4] "Several poxviruses encode a soluble IFN receptor homologue that acts as a decoy to inhibit the biological activity of IFN," and that activity is for IFN to "bind to their cognate recepors on the cell surface to iniate a signaling cascade, known as the Janus kinase(JAK)-signal transducer and activation of transcription(Stat) pathways.^[3] For example, in a study done by a group of researcher, they found that the B18R protein, which acts as a type 1 IFN receptor and is produced by the vaccinia virus, it was found that the B18R protein inhibited IFN's ability to begin the phosphorylation of JAK1 which reduced the antiviral effect of IFN.^[5]

Some viruses can encode proteins that bind to dsRNA. In a study where the researchers infected Human U cells with reovirus-sigma3 protein and then, using the Western blot test, they found that reaovirus-sigma3 protein does bind to dsRNA.^[6] Along with that, another study in which the researchers infected mouse L cells with vaccinia virus E3L found that E3L encodes the p25 protein that binds to dsRNA.^[7] Without double stranded RNA (dsRNA), because it is bound to by the proteins, it is not able to create IFN-induced PKR and 2'-5' oligoadenylate-synthetase making IFN ineffective.^[8] It was also found that JEV was able to inhibit IFN-alpha's ability to activate or create ISGs such as PKR.^[3] PKR was not able to be found in the JEV infected cells and PKR RNA levels were found to be lower in those same infected cells, and this disruption of PKR can occur, for example, in cells infected with flavaviruses.^[3]

The H5N1 influenza virus, also known as bird flu, has been shown to have resistance to interferon and other anti-viral cytokines. This is part of the reason for its high mortality rates in humans. It is resistant due to a single amino acid mutation in Non-Structual protein 1 (NS1), the precise mechanism of how this confers immunity is unclear (reference is Lethal H5N1 influenza viruses escape host anti-viral cytokine responses, Sang Heui Seo, Nature Med, 2002).

Pharmaceutical uses

Three vials filled with human leukocyte interferon.

Image File history File links Download high resolution version (3512x2634, 293 KB) Title: Interferon Image ID: 3549 Photographer: Unknown Restrictions: Public Domain Image Date: 6/1/1982 [1] File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... Image File history File links Download high resolution version (3512x2634, 293 KB) Title: Interferon Image ID: 3549 Photographer: Unknown Restrictions: Public Domain Image Date: 6/1/1982 [1] File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ...

Uses

Just as their natural function, interferons have antiviral, antiseptic and antioncogenic properties when administered as drugs.

Interferon therapy is used (in combination with chemotherapy and radiation) as a treatment for many cancers.

More than half of hepatitis C patients treated with interferon respond with better blood tests and better liver biopsies. There is some evidence that giving interferon immediately following infection can prevent hepatitis C; however, people infected by hepatitis C often do not display symptoms of HCV until months or years later. This page is for the disease. ...

Interferon is also used in the treatment and control of the neurological disorder multiple sclerosis, an autoimmune disorder. Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ...

Administered intranasally in very low doses, interferon is extensively used in Eastern Europe and Russia as a method to prevent and treat viral respiratory diseases such as cold and flu. However, mechanisms of such action of interferon are not well understood; it is thought that doses must be larger by several orders of magnitude to have any effect on the virus. Consequently, most Western scientists are skeptical of any claims of good efficacy.^[9] // Acute viral nasopharyngitis, or acute coryza, usually known as the common cold, is a highly contagious, viral infectious disease of the upper respiratory system, primarily caused by picornaviruses or coronaviruses. ... Respiratory disease properly named influenza(say: in-floo-en-zah ). Some specific varities of influenza with a vaccination available are: A-New Caledonia, A-California, B-Shanghai. ...

Route of administration

When used in the systemic therapy, IFN-α and IFN-γ are mostly administered by an intramuscular injection. The injection of interferons in the muscle, in the vein, or under skin is generally well tolerated.

Interferon alpha can also be induced with small imidazoquinoline molecules by activation of TLR7 receptor. Aldara (Imiquimod) cream works with this mechanism to induce IFN alpha and IL12 and approved by FDA to treat Actinic Keratosis, Superficial Basal Cell Carcinoma, and External Genital Warts. Imidazoquinoline, and locations of possible modification to form its derivatives. ...

Adverse effects

The most frequent adverse effects are flu-like symptoms: increased body temperature, feeling ill, fatigue, headache, muscle pain, convulsion, dizziness, hair thinning, and depression. Erythema, pain and hardness on the spot of injection are also frequently observed. Interferon therapy causes immunosuppression and can result in some infections manifesting in unusual ways.^[10] ... Immunosuppression is the medical suppression of the immune system. ...

All known adverse effects are usually reversible and disappear a few days after the therapy has been finished.

Types

Several different types of interferon are now approved for use in humans.

More recently, the FDA approved pegylated interferon-alpha, in which polyethylene glycol is added to make the interferon last longer in the body. (Pegylated interferon-alpha-2b was approved in January 2001; pegylated interferon-alpha-2a was approved in October 2002.) The pegylated form is injected once weekly, rather than three times per week for conventional interferon-alpha. Used in combination with the antiviral drug ribavirin, pegylated interferon produces sustained cure rates of 75% or better in people with genotype 2 or 3 hepatitis C (which is easier to treat) but still less than 50% in people with genotype 1 (which is most common in the U.S. and Western Europe). Polyethylene glycol (PEG) and polyethylene oxide are polymers of ethylene oxide. ... Polyethylene glycol (PEG) and polyethylene oxide (PEO) are polymers composed of repeating subunits of identical structure, called monomers, and are the most commercially important polyethers. ... Pegylated interferon-alpha-2b is a treatment for hepatitis C developed by Roche. ... Pegylated interferon alfa 2a (40KD) (commercial name PEGASYS) is an antiviral drug discovered at the pharmaceutical company F.Hoffmann-La Roche; it has a dual mode of action - both antiviral and on the immune system. ... Antiviral drugs are a class of medication used specifically for treating viral infections. ... Ribavirin (Copegus®; Rebetol®; Ribasphere®; Vilona®,Virazole®, also generics from Sandoz, Teva, Warrick) is an anti-viral drug which is active against a number of DNA and RNA viruses. ...

Interferon-beta (Interferon beta-1a and Interferon beta-1b) is used in the treatment and control of multiple sclerosis. By an as-yet-unknown mechanism, interferon-beta inhibits the production of Th1 cytokines and the activation of monocytes. Interferon beta-1a is a drug in the interferon family used to treat multiple sclerosis. ... Interferon beta-1b (marketed as Betaseron) is a drug in the interferon family used to treat multiple sclerosis. ...

History

While aiming to develop an improved vaccine for smallpox, two Japanese virologists, Yasu-ichi Nagano and Yasuhiko Kojima working at the the Institute for Infectious Diseases at the University of Tokyo, noticed that rabbit-skin or testis previously inoculated with UV-inactivated virus exhibited inhibition of viral growth when re-infected at the same site with live virus. They hypothesised that this was due to some inhibitory factor, and began to characterise it by fractionation of the UV-irradiated viral homogenates using an ultracentrifuge. They published these findings in 1954 in the French journal now known as “Journal de la Société de Biologie”.^[11] While this paper demonstrated that the activity could be separated from the virus particles, it could not reconcile the antiviral activity demonstrated in the rabbit skin experiments, with the observation that the same supernatant led to the production of antiviral antibodies in mice. A further paper in 1958, involving triple-ultracentrifugation of the homogenate demonstrated that the inhibitory factor was distinct from the virus particles, leading to trace contamination being ascribed to the 1954 observations.^[12][13] A vaccine is an antigenic preparation used to establish immunity to a disease. ... Smallpox (also known by the Latin names Variola or Variola vera) is a contagious disease unique to humans. ... Virology, often considered a part of microbiology or of pathology, is the study of organic viruses: their structure and classification, their ways to infect and exploit cells to reproduce and cause disease, the techniques to isolate and culture them, and their potential uses in research and therapy. ... “Todai” redirects here. ... Inoculation was a method of minimising the harm done by infection with smallpox. ... Fractional distillation is the separation of a mixture of compounds by their boiling point, by heating to high enough temperatures. ... Categories: Move to Wiktionary | Biochemistry stubs ... The ultracentrifuge is a centrifuge optimized for spinning a rotor at very high speeds, capable of generating acceleration as high as 1,000,000 G (9,800 km/s²) There are two kinds of ultracentrifuges, the preparative and the analytical ultracentrifuge. ... Supernatant is adjective for any liquid above non-soluble solids/precipitates and it means floating above (see http://www. ... Wikipedia does not yet have an article with this exact name. ...

Meanwhile, the British virologist Alick Isaacs and the Swiss researcher Jean Lindenmann, at the National Institute for Medical Research in London, noticed an interference effect caused by heat-inactivated influenza virus on the growth of live influenza virus in chicken egg membranes in a nutritive solution chorioallantoic membrane. They published their results in 1957;^[14] in this paper they coined the term ‘interferon’, and today that specific interfering agent is known as a ‘Type I interferon’.^[15] Alick Isaacs ( - 1967) was a British virologist. ... The National Institute For Medical Research, commonly abbreviated to NIMR, is a large medical research facility situated in rural Mill Hill, England, on the outskirts of London. ... Negatively stained flu virions. ...

Nagano’s work was never fully appreciated in the scientific community; possibly because it was printed in French, but also because his in vivo system was perhaps too complex to provide clear results in the characterisation and purification of interferon. As time passed, Nagano became aware that his work had not been widely recognised, yet did not actively seek revaluation of his status in field of interferon research. As such, the majority of the credit for discovery of the interferon goes to Isaacs and Lindenmann, with whom there is no record of Nagano ever having made personal contact.^[16] In vivo (Latin for (with)in the living). ...

As a drug

Interferon was scarce and expensive until 1980 when the interferon gene was inserted into bacteria using recombinant DNA technology, allowing mass cultivation and purification from bacterial cultures.^[17] For other uses, see Gene (disambiguation). ... Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ... Recombinant DNA technology adds/replaces DNA in an organism resulting in the recipient organism containing exogenous DNA. Recombinant proteins are proteins that are produced by different genetically modified organisms following insertion of the relevant DNA into their genome. ... Tillage (American English), or cultivation (UK) is the agricultural preparation of the soil to receive seeds. ...

Trivia

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• Interferon is species-specific: the substance prepared from infected eggs protected only chicken cells from virus infection, while the similar substance prepared from mice protected only mouse cells.
• Produced by many cells in the human body by a receptor dependent feedback mechanism.
• Interferons are part of the "first-wave" immune response of the innate immune system, acting within hours, whereas antibody production takes days.^{[citation needed]}
• Global sales ~ 5 billion US $. The second most successful pharmaceutical ever to come from genetic engineering.
• A book was written about it: Toine Pieters, Interferon: The Science and Selling of a Miracle Drug (London: Routledge, 2005), xiv+264 pp., ISBN: 0-415-34246-5
• There are two types of IFNs: Type I (binding to IFN-aR1 and IFN-aR2c receptors; IFNAR1 chain is not the major ligand-binding chain), and type II (binding to IFN-gammaR1 and IFN-gammaR2 receptors).
• In general, exposure of human cells to viruses or double stranded RNAs induces the production of IFN-a, IFN-b, and IFN-o species.
• For the most part, the IFN-alpha species are not glycosylated, although some contain carbohydrates.
• The IFN-alpha family represents a family of related and homologous proteins, each exhibiting a unique activity profile. Each IFN-a species seems to exhibit a distinct profile of activities [antiviral, antiproliferative, and stimulation of cytotoxic activities of natural killer (NK) cells and T cells]
• The IFNs and IFN-like molecules signal through the Jak-Stat pathway. The receptor for the Type I IFNs consists of two chains, IFN-aR1 and IFN-aR2c. The ligand INF-alpha is a monomer that binds to the two-chain complex of IFN-aR1 and INF-aR2c.
• Within each subtype of mammalian Type I IFN, there is additional variability in gene duplication. The IFN-a genes are duplicated to a much greater extent than any other subtype of Type I IFN. This observation in conjunction with the observation that the IFN-a subtypes generally possess the highest specific antiviral activity imply that physiologically, the body likely uses IFN-a as the primary antiviral defense protein and that the major function of IFN-a is defense.
• STRUCTURE: The Type I IFNs consist of five a-helices (labeled A–E) which are linked by one overhand loop (AB loop) and three shorter segments (BC, CD, and DE loops). Helices A, B, C, and E are arranged in an antiparallel fashion to form a left-handed four-helix bundle. The AB loop contains short segments of 3_10 helix and is best described in three segments labeled AB1, AB2, and AB3. In all Type I IFNs, the AB1 loop encircles and is linked to helix E by a disulfide bond. An additional disulfide bond is observed in most IFN-a subtypes but not IFN-b, which connects the N-terminus of the molecule to helix C. The AB loop is critical for high-affinity IFNAR2 binding and suggest that sequence differences in this region may hold the key to differences in biological activity between the different IFN-a subtypes.
• The NMR structure of IFNAR2 has been determined and exhibits the same general structure as IFN-gammaR1. However, the interdomain angle is approximately 90 degrees rather than 120 degrees. Only loops in N-terminal domain (L2–L4) have been shown to be important for IFN-a2 binding.
• The IFNs were the first of the proteins we now recognize as members of the Class II cytokine family.
• IFNa2 contain 165 amino acids; according to circular dichroism measurements ~68% of the residues adopt helical conformation.INFa2 is composed of five a-helices, labeled A–E, linked by one long overhand connection (AB loop) and three short segments (BC, CD and DE loops). The topology of the molecule resembles the classical up-up-down-down four-helixbundle motif; helices A, B, C, and E comprise the helix bundle.
• Type I IFNs are stable at acidic pH (pH 2) and are represented by two major subtypes, the fibroblast or beta interferon (IFN-b) and the leukocyte or alpha family of interferons (IFN-a).The only known interferon of type II is IFN-g, which is produced exclusively by lymphocytes.

Image File history File links Broom_icon. ... Image File history File links Broom_icon. ...

Pharmaceutical forms of interferons in the market

• Rebif, liquid form of Interferon beta 1a
• Avonex, lyophilized form of Interferon beta 1a
• Cinnovex, generic/biosimilar form of Interferon beta 1a (Avonex)
• Betaseron, Interferon beta 1b
• Roferon A. regular Interferon-alpha2a
• Intron-A, regular Interferon-alpha2b
• PEGASYS, Pegylated Interferon alpha 2a
• Berlex, Interferon beta 1b
• PegIntron, Pegylated Interferon alpha 2b
• Reiferon Etard , pegylated Interferon alpha 2a

Interferon beta-1a is a drug in the interferon family used to treat multiple sclerosis. ... Avonex is an interferon drug developed by the Biogen Idec pharmaceutical company for use in the treatment of relapsing/recurring Multiple Sclerosis. ... // CinnoVex is the trade name of recombinant Interferon beta 1-a, which is manufacturing as biosimilar/biogeneric in Iran. ... Betaseron (interferon beta-1B) is a drug used in the treatment of multiple sclerosis. ... Pegylated interferon alfa 2a (40KD) (commercial name PEGASYS) is an antiviral drug discovered at the pharmaceutical company F.Hoffmann-La Roche; it has a dual mode of action - both antiviral and on the immune system. ... // Berlex Laboratories, Incorporated is a research-based pharmaceutical company headquartered in Montville, New Jersey with operations in Wayne, New Jersey; Bothell, Washington; Seattle, Washington; and Richmond, California. ...

See also

• Immunotherapy
• Immunosuppression
• Immunosuppressive drug
• PEGASYS
• CinnoVex
• ATC code L03#L03AB Interferons
• PEGylation

The term immunotherapy incorporates an array of strategies of treatment based upon the concept of modulating the immune system to achieve a prophylactic and/or therapeutic goal. ... Immunosuppression is the medical suppression of the immune system. ... For a list of immunosuppressive drugs, see the transplant rejection page. ... Pegylated interferon alfa 2a (40KD) (commercial name PEGASYS) is an antiviral drug discovered at the pharmaceutical company F.Hoffmann-La Roche; it has a dual mode of action - both antiviral and on the immune system. ... // CinnoVex is the trade name of recombinant Interferon beta 1-a, which is manufacturing as biosimilar/biogeneric in Iran. ... A section of the Anatomical Therapeutic Chemical Classification System. ... Polyethylene glycol // In 1970s, pioneering research by Davis, Abuchowski and colleagues foresaw the potential of the conjugation of Polyethylene glycol (PEG) to Proteins. ...

References

Pestka S. et al, Immun Rev, (2004) 202, pp. 8-32 A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...