Interferon - Knowledge

1906:(VIF). It took another fifteen to twenty years, using somatic cell genetics, to show that the interferon action gene and interferon gene reside in different human chromosomes. The purification of human beta interferon did not occur until 1977. Y.H. Tan and his co-workers purified and produced biologically active, radio-labeled human beta interferon by superinducing the interferon gene in fibroblast cells, and they showed its active site contains tyrosine residues. Tan's laboratory isolated sufficient amounts of human beta interferon to perform the first amino acid, sugar composition and N-terminal analyses. They showed that human beta interferon was an unusually hydrophobic glycoprotein. This explained the large loss of interferon activity when preparations were transferred from test tube to test tube or from vessel to vessel during purification. The analyses showed the reality of interferon activity by chemical verification. The purification of human alpha interferon was not reported until 1978. A series of publications from the laboratories of 36: 1867:. Viral interference refers to the inhibition of virus growth caused by previous exposure of cells to an active or a heat-inactivated virus. Isaacs and Lindenmann were working with a system that involved the inhibition of the growth of live influenza virus in chicken embryo chorioallantoic membranes by heat-inactivated influenza virus. Their experiments revealed that this interference was mediated by a protein released by cells in the heat-inactivated influenza virus-treated membranes. They published their results in 1957 naming the antiviral factor they had discovered 1312: 1833: 235: 831:—also induced by interferon action—destroys RNA within the cells to further reduce protein synthesis of both viral and host genes. Inhibited protein synthesis impairs both virus replication and infected host cells. In addition, interferons induce production of hundreds of other proteins—known collectively as interferon-stimulated genes (ISGs)—that have roles in combating viruses and other actions produced by interferon. They also limit viral spread by increasing 1446: 1736: 1946:. Interferon can also be produced by recombinant mammalian cells. Before the early 1970s, large scale production of human interferon had been pioneered by Kari Cantell. He produced large amounts of human alpha interferon from large quantities of human white blood cells collected by the Finnish Blood Bank. Large amounts of human beta interferon were made by superinducing the beta interferon gene in human fibroblast cells. 6250: 9509: 9497: 1402:(SNP) in the gene encoding the type III interferon IFN-λ3 was found to be protective against chronic infection following proven HCV infection and predicted treatment response to interferon-based regimens. The frequency of the SNP differed significantly by race, partly explaining observed differences in response to interferon therapy between European-Americans and African-Americans. 1699:; at least 75% of people with hepatitis C genotypes 2 or 3 benefit from interferon treatment, although this is effective in less than 50% of people infected with genotype 1 (the more common form of hepatitis C virus in both the U.S. and Western Europe). Interferon-containing regimens may also include 1373:

can be treated with IFN-α, often in combination with other antiviral drugs. Some of those treated with interferon have a sustained virological response and can eliminate hepatitis virus in the case of hepatitis C. The most common strain of hepatitis C virus (HCV) worldwide—genotype I— can be treated

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Many viruses have evolved mechanisms to resist interferon activity. They circumvent the IFN response by blocking downstream signaling events that occur after the cytokine binds to its receptor, by preventing further IFN production, and by inhibiting the functions of proteins that are induced by IFN.

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Interferons can disrupt signaling by other stimuli. For example, interferon alpha induces RIG-G, which disrupts the CSN5-containing COP9 signalosome (CSN), a highly conserved multiprotein complex implicated in protein deneddylation, deubiquitination, and phosphorylation. RIG-G has shown the capacity

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In general, type I and II interferons are responsible for regulating and activating the immune response. Expression of type I and III IFNs can be induced in virtually all cell types upon recognition of viral components, especially nucleic acids, by cytoplasmic and endosomal receptors, whereas type II

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Cantell's and Tan's methods of making large amounts of natural interferon were critical for chemical characterisation, clinical trials and the preparation of small amounts of interferon messenger RNA to clone the human alpha and beta interferon genes. The superinduced human beta interferon messenger

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genotype I to interferon-based therapy has been attributed in part to homology between viral envelope protein E2 and host protein kinase R, a mediator of interferon-induced suppression of viral protein translation, although mechanisms of acquired and intrinsic resistance to interferon therapy in HCV

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and Alan Waldman between 1978 and 1981, describe the purification of the type I interferons IFN-α and IFN-β. By the early 1980s, genes for these interferons had been cloned, adding further definitive proof that interferons were responsible for interfering with viral replication. Gene cloning also

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All interferons share several common effects: they are antiviral agents and they modulate functions of the immune system. Administration of Type I IFN has been shown experimentally to inhibit tumor growth in animals, but the beneficial action in human tumors has not been widely documented. A

1954:. to clone the human beta interferon gene in bacteria and the recombinant interferon was developed as 'betaseron' and approved for the treatment of MS. Superinduction of the human beta interferon gene was also used by Israeli scientists to manufacture human beta interferon. 1213:

encode soluble IFN receptor homologs—like the B18R protein of the vaccinia virus—that bind to and prevent IFN interacting with its cellular receptor, impeding communication between this cytokine and its target cells. Some viruses can encode proteins that bind to

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virus-infected cell releases viral particles that can infect nearby cells. However, the infected cell can protect neighboring cells against a potential infection of the virus by releasing interferons. In response to interferon, cells produce large amounts of an

1413:) followed by interferon drops is an effective treatment approach for these types of eye infections. Unconfirmed results suggested that the combination of interferon and an antiviral agent may speed the healing process compared to antiviral therapy alone. 1084:

initiate gene transcription by binding to IFN-activated site (GAS) elements in gene promoters. Type I IFNs can induce expression of genes with either ISRE or GAS elements, but gene induction by type II IFN can occur only in the presence of a GAS element.

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More than twenty distinct IFN genes and proteins have been identified in animals, including humans. They are typically divided among three classes: Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all three classes are important for fighting

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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 (September 2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance".

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Dunn, Gavin P.; Bruce, Allen T.; Sheehan, Kathleen C. F.; Shankaran, Vijay; Uppaluri, Ravindra; Bui, Jack D.; Diamond, Mark S.; Koebel, Catherine M.; Arthur, Cora (July 2007). "A critical function for type I interferons in cancer immunoediting".

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adopts using its sigma 3 (σ3) protein, and vaccinia virus employs using the gene product of its E3L gene, p25. The ability of interferon to induce protein production from interferon stimulated genes (ISGs) can also be affected. Production of

866:, while the immunoproteasome processes these peptides for loading onto the MHC I molecule, thereby increasing the recognition and killing of infected or malignant cells. Higher MHC II expression increases presentation of these peptides to 724:

on target cells, which leads to expression of proteins that will prevent the virus from producing and replicating its RNA and DNA. Overall, IFN-α can be used to treat hepatitis B and C infections, while IFN-β can be used to treat multiple

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can also produce large amounts of type I interferons when stimulated by viral molecular patterns. The production of type I IFN-α is inhibited by another cytokine known as Interleukin-10. Once released, type I interferons bind to the

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Laghari ZA, Chen SN, Li L, Huang B, Gan Z, Zhou Y, Huo HJ, Hou J, Nie P (2018). "Functional, signalling and transcriptional differences of three distinct type I IFNs in a perciform fish, the mandarin fish Siniperca chuatsi".

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Navratil V, de Chassey B, Meyniel L, Pradezynski F, André P, Rabourdin-Combe C, Lotteau V (July 2010). "System-level comparison of protein-protein interactions between viruses and the human type I interferon system network".

1902:'s lab, observed in 1957 that attenuated poliovirus conferred a species specific anti-viral effect in human amniotic cell cultures. They described these observations in a 1959 publication, naming the responsible factor 5587:

Okamura H, Berthold W, Hood L, Hunkapiller M, Inoue M, Smith-Johannsen H, Tan YH (August 1980). "Human fibroblastoid interferon: immunosorbent column chromatography and N-terminal amino acid sequence".

1688:) followed in October 2002. These PEGylated drugs are injected once weekly, rather than administering two or three times per week, as is necessary for conventional interferon-alpha. When used with the 3391:"Proteolytic cleavage of the reovirus sigma 3 protein results in enhanced double-stranded RNA-binding activity: identification of a repeated basic amino acid motif within the C-terminal binding region" 1072:. Binding of ISGF3 and other transcriptional complexes activated by IFN signaling to these specific regulatory elements induces transcription of those genes. A collection of known ISGs is available on 612:. However, virus-encoded genetic elements have the ability to antagonize the IFN response, contributing to viral pathogenesis and viral diseases. IFNs also have various other functions: they activate 1894:

with UV-inactivated virus. They hypothesised that some "viral inhibitory factor" was present in the tissues infected with virus and attempted to isolate and characterize this factor from tissue

785:(also called CRF2-12). Although discovered more recently than type I and type II IFNs, recent information demonstrates the importance of Type III IFNs in some types of virus or fungal infections. 977:

technology tools such as siRNA or vector-based reagents can either silence or stimulate interferon pathways. Release of IFN from cells (specifically IFN-γ in lymphoid cells) is also induced by

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When used in systemic therapy, IFNs are mostly administered by an intramuscular injection. The injection of IFNs in the muscle or under the skin is generally well tolerated. The most frequent

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Xu GP, Zhang ZL, Xiao S, Zhuang LK, Xia D, Zou QP, Jia PM, Tong JH (March 2013). "Rig-G negatively regulates SCF-E3 ligase activities by disrupting the assembly of COP9 signalosome complex".

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Nagata S, Taira H, Hall A, Johnsrud L, Streuli M, Ecsödi J, Boll W, Cantell K, Weissmann C (March 1980). "Synthesis in E. coli of a polypeptide with human leukocyte interferon activity".

6665: 5033: 1339:. This treatment may help in reducing attacks in relapsing-remitting multiple sclerosis and slowing disease progression and activity in secondary progressive multiple sclerosis. 862:

also significantly stimulates the MHC II-dependent presentation of antigens. Higher MHC I expression increases presentation of viral and abnormal peptides from cancer cells to

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that regulate the expression of certain immune system genes. Some STATs are activated by both type I and type II IFNs. However each IFN type can also activate unique STATs.

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Furthermore, others may have made observations on interferons before the 1957 publication of Isaacs and Lindenmann. For example, during research to produce a more efficient

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In addition to the JAK-STAT pathway, IFNs can activate several other signaling cascades. For instance, both type I and type II IFNs activate a member of the CRK family of

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Zoon KC, Smith ME, Bridgen PJ, Anfinsen CB, Hunkapiller MW, Hood LE (February 1980). "Amino terminal sequence of the major component of human lymphoblastoid interferon".

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Production of interferons occurs mainly in response to microbes, such as viruses and bacteria, and their products. Binding of molecules uniquely found in microbes—viral

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disease. Application of IFN-I prior to (or in the very early stages of) viral infection can be protective, which should be validated in randomized clinical trials.

1231:, for example, can be disrupted in cells infected with JEV. Some viruses escape the anti-viral activities of interferons by gene (and thus protein) mutation. The 5623:

Knight E, Hunkapiller MW, Korant BD, Hardy RW, Hood LE (February 1980). "Human fibroblast interferon: amino acid analysis and amino terminal amino acid sequence".

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Ekins, S.; Lingerfelt, M. A.; Comer, J. E.; Freiberg, A. N.; Mirsalis, J. C.; O'Loughlin, K.; Harutyunyan, A.; McFarlane, C.; Green, C. E.; Madrid, P. B. (2018).

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Ikeda, Hiroaki; Old, Lloyd J.; Schreiber, Robert D. (April 2002). "The roles of IFN gamma in protection against tumor development and cancer immunoediting".

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Several different types of interferons are approved for use in humans. One was first approved for medical use in 1986. For example, in January 2001, the

8576: 1757: 1750: 1114:(MAP kinase) to induce gene transcription. Antiviral and antiproliferative effects specific to type I IFNs result from p38 MAP kinase signaling. The 1420:

are flu-like symptoms: increased body temperature, feeling ill, fatigue, headache, muscle pain, convulsion, dizziness, hair thinning, and depression.

8632: 8526: 3350:"Structural requirements of double-stranded RNA for the activation of 2',5'-oligo(A) polymerase and protein kinase of interferon-treated HeLa cells" 9334: 8658: 7815: 5784:

Nagata S, Mantei N, Weissmann C (October 1980). "The structure of one of the eight or more distinct chromosomal genes for human interferon-alpha".

4167:"Practical guidelines for the management of interferon-alpha-2b side effects in patients receiving adjuvant treatment for melanoma: expert opinion" 9120: 1242:

change in its Non-Structural Protein 1 (NS1), although the precise mechanism of how this confers immunity is unclear. The relative resistance of

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Borden, Ernest C.; Sen, Ganes C.; Uze, Gilles; Silverman, Robert H.; Ransohoff, Richard M.; Foster, Graham R.; Stark, George R. (December 2007).

1271: 1263: 3301:"The vaccinia virus soluble alpha/beta interferon (IFN) receptor binds to the cell surface and protects cells from the antiviral effects of IFN" 2547:

Espinosa V, Dutta O, McElrath C, Du P, Chang YJ, Cicciarelli B, Pitler A, Whitehead I, Obar JJ, Durbin JE, Kotenko SV, Rivera A (October 2017).

8795: 8653: 8622: 8586: 6865: 5023: 2086: 707:) can be produced by all nucleated cells when they recognize that a virus has invaded them. The most prolific producers of IFN-α and IFN-β are 4506:"Secondary prevention of recurrence by interferon therapy after ablation therapy for hepatocellular carcinoma in chronic hepatitis C patients" 8708: 8673: 7887: 9445: 9140: 8749: 8739: 8729: 8663: 8612: 5367:

Meager A, Graves H, Burke DC, Swallow DM (August 1979). "Involvement of a gene on chromosome 9 in human fibroblast interferon production".

3577:"Hepatitis C Virus Envelope Protein E2 Does Not Inhibit PKR by Simple Competition with Autophosphorylation Sites in the RNA-Binding Domain" 1926:, one amino acid at a time. He later won the Nobel Prize in chemistry. Interferon was scarce and expensive until 1980, when the interferon 1342:

Interferon therapy is used (in combination with chemotherapy and radiation) as a treatment for some cancers. This treatment can be used in

1080:); Additionally, STAT homodimers or heterodimers form from different combinations of STAT-1, -3, -4, -5, or -6 during IFN signaling; these 4790: 9374: 9364: 9354: 9291: 9016: 8719: 1044:. As a result, an IFN-stimulated gene factor 3 (ISGF3) complex forms—this contains STAT1, STAT2 and a third transcription factor called 9369: 9286: 9251: 8996: 8768: 8501: 8419: 3540:

Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM (1999). "Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein".

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confirmed that IFN-α was encoded by a family of many related genes. The type II IFN (IFN-γ) gene was also isolated around this time.

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Weissenbach J, Chernajovsky Y, Zeevi M, Shulman L, Soreq H, Nir U, Wallach D, Perricaudet M, Tiollais P, Revel M (December 1980).

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in humans): This is also known as immune interferon and is activated by Interleukin-12. Type II interferons are also released by

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Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T (July 2003).

2091: 2081: 2076: 2071: 2066: 2061: 2056: 1772: 1069: 8602: 8412: 6816: 6222: 5965: 5161: 3440:"The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase" 2118: 778: 308: 129: 5269:"The linkage of genes for the human interferon-induced antiviral protein and indophenol oxidase-B traits to chromosome G-21" 4889:

Sharieff KA, Duncan D, Younossi Z (February 2002). "Advances in treatment of chronic hepatitis C: 'pegylated' interferons".

4249:"Combination therapy (interferon alfa and ribavirin) in the treatment of chronic hepatitis C: a rapid and systematic review" 3497:

Seo SH, Hoffmann E, Webster RG (September 2002). "Lethal H5N1 influenza viruses escape host anti-viral cytokine responses".

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Whitehead KA, Dahlman JE, Langer RS, Anderson DG (2011). "Silencing or stimulation? siRNA delivery and the immune system".

1110: 1779: 1274:, which itself is a weak IFN-I inducer in human cells. SARS-CoV-2 limits the IFN-III response as well. Reduced numbers of 1238:

virus, also known as bird flu, has resistance to interferon and other anti-viral cytokines that is attributed to a single

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With pegylated IFN lambda, the relative risk for hospitalization with the Omicron strains is reduced by about 80 %.

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Elrefaey, Ahmed M. E.; Hollinghurst, Philippa; Reitmayer, Christine M.; Alphey, Luke; Maringer, Kevin (November 2021).

1089: 1032:) signaling pathway. In this pathway, JAKs associate with IFN receptors and, following receptor engagement with IFN, 9420: 8177: 6342: 3881: 1819: 1700: 1485: 823:

in response to new viral infections; the phosphorylated eIF-2 forms an inactive complex with another protein, called

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Liu YJ (2005). "IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors".

9131: 8833: 1768: 1467: 1399: 721: 676: 3211:"Blocking of the alpha interferon-induced JAK-STAT signaling pathway by Japanese encephalitis virus infection" 2693:"Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence" 489: 368: 201: 7484: 6260: 5316:

Tan YH (March 1976). "Chromosome 21 and the cell growth inhibitory effect of human interferon preparations".

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Kidd, P (2003). "Th1/Th2 Balance: the hypothesis, its limitations, and implications for health and disease".

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to inhibit NF-κB and STAT3 signaling in lung cancer cells, which demonstrates the potential of type I IFNs.

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Pawlotsky, Jean-Michel (2003). "The nature of interferon-alpha resistance in hepatitis C virus infection".

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interferon is induced by cytokines such as IL-12, and its expression is restricted to immune cells such as

743:. However, they block the proliferation of type-2 T helper cells. The previous results in an inhibition of 1405:

Unconfirmed results suggested that interferon eye drops may be an effective treatment for people who have

8320: 7870: 7645: 1463: 1275: 1077: 994: 954: 708: 321: 98: 9487: 9425: 9067: 8353: 8155: 7865: 7181: 4813:"Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3?" 4675:"Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis" 1935: 1871:. The findings of Isaacs and Lindenmann have been widely confirmed and corroborated in the literature. 485: 364: 197: 6040: 5937: 5668:"Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia coli cloning studies" 1128:, which is involved in protein synthesis; and phosphorylates a translational repressor protein called 9026: 8274: 7959: 4122:

Goldstein D, Laszlo J (Sep 1988). "The role of interferon in cancer therapy: a current perspective".

3931:"Type I and Type III Interferons - Induction, Signaling, Evasion, and Application to Combat COVID-19" 2639:

de Veer MJ, Holko M, Frevel M, Walker E, Der S, Paranjape JM, Silverman RH, Williams BR (June 2001).

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De Andrea M, Ravera R, Gioia D, Gariglio M, Landolfo S (2002). "The interferon system: an overview".

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Reis G, Moreira Silva EA, Medeiros Silva DC, Thabane L, Campos VH, Ferreira TS, et al. (2023).

2500:"Interferon-λ in the context of viral infections: production, response and therapeutic implications" 1409:, a type of eye infection. There is no clear evidence to suggest that removing the infected tissue ( 154: 9534: 8309: 7736: 7712: 6315: 1895: 1680:

is linked to the interferon molecule to make the interferon last longer in the body. Approval for

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STAT activation initiates the most well-defined cell signaling pathway for all IFNs, the classical

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Rice, G. P.; Incorvaia, B.; Munari, L.; Ebers, G.; Polman, C.; D'Amico, R.; Filippini, G. (2001).

675:: All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α/β receptor ( 8779: 8475: 7304: 6821: 6268: 1746: 1634: 1456: 1793: 35: 9164: 7637: 7063: 7015: 6436: 4774: 3935: 1915: 1424:, pain, and hardness at the site of injection are also frequently observed. IFN therapy causes 858:

activity. All interferons significantly enhance the presentation of MHC I dependent antigens.

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Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. (2013).

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Hauschild A, Gogas H, Tarhini A, Middleton MR, Testori A, Dréno B, Kirkwood JM (March 2008).

2939: 2340: 1681: 1669: 1644: 1624: 1613: 1603: 1170: 1166: 1150: 6850: 2742:"DNA Damage Signaling and p53-dependent Senescence after Prolonged β-Interferon Stimulation" 1120:(PI3K) signaling pathway is also regulated by both type I and type II IFNs. PI3K activates 604:

that help eradicate pathogens. Interferons are named for their ability to "interfere" with

9091: 8927: 8163: 6712: 6569: 5994: 5895: 5844: 5793: 5738: 5679: 5632: 5553: 5376: 5325: 5221: 5066: 4626: 4572: 3827: 3451: 2704: 1899: 1259: 1186: 1125: 1018: 839:. The effect of IFN on p53 is also linked to its protective role against certain cancers. 700: 625: 600:, molecules used for communication between cells to trigger the protective defenses of the 468: 347: 180: 20: 668:

through which they signal, human interferons have been classified into three major types.

8: 9042: 8932: 8824: 8005: 6951: 6698: 6661: 6413: 4080:"Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis" 1887: 1677: 1593: 1532: 1522: 1347: 1336: 1215: 902: 774: 617: 6609: 5998: 5899: 5848: 5797: 5742: 5683: 5636: 5557: 5420:"Chemical modifications of tyrosyl residue(s) and action of human-fibroblast interferon" 5380: 5329: 5225: 5070: 4630: 4576: 3627: 3455: 2708: 313: 9529: 8956: 8951: 8917: 8912: 8858: 8446: 8438: 8172: 8129: 8044: 7751: 7297: 6763: 6233: 6178: 6151: 6132: 6088: 5919: 5868: 5817: 5461:"Purification and in vitro labeling of interferon from a human fibroblastoid cell line" 5436: 5419: 5400: 5349: 5293: 5268: 5090: 5028: 4999: 4974: 4839: 4812: 4750: 4723: 4699: 4674: 4650: 4593: 4556: 4532: 4505: 4440: 4415: 4414:

Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, et al. (2011).

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Poordad F, McCone Jr J, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. (2011).

4342: 4315: 4224: 4207: 4147: 4096: 4079: 4055: 4030: 4006: 3981: 3957: 3930: 3903: 3876: 3849: 3822: 3798: 3769: 3745: 3716: 3692: 3522: 3316: 3108: 3083: 3064: 2995: 2970: 2951: 2903: 2878: 2856: 2766: 2741: 2670: 2641:"Functional classification of interferon-stimulated genes identified using microarrays" 2621: 2573: 2548: 2524: 2499: 2466: 2439: 2388: 2363: 2260: 2233: 2214: 2160: 1864: 1840: 1583: 1572: 1561: 1550: 1332: 1328: 1324: 1174: 1061: 938: 728: 585:. In a typical scenario, a virus-infected cell will release interferons causing nearby 6017: 5982: 5761: 5726: 5702: 5667: 5521: 5504: 5477: 5460: 5244: 5209: 4950: 4925: 3603: 3576: 3415: 3390: 3366: 3349: 3325: 3300: 3235: 3210: 2805: 2202: 9384: 8435: 8036: 7655: 7521: 7278: 7233: 6934: 6218: 6183: 6124: 6080: 6043:, Ho M, Armstrong JA, Ke YH, Tan YH, "Interferon Production", issued 1973 6022: 5961: 5911: 5860: 5809: 5766: 5707: 5648: 5605: 5569: 5526: 5482: 5441: 5392: 5341: 5298: 5249: 5190: 5157: 5134: 5094: 5082: 5004: 4955: 4906: 4871: 4844: 4780: 4755: 4704: 4642: 4598: 4537: 4486: 4445: 4396: 4347: 4316:"Efficacy and safety of telaprevir in patients with genotype 1 hepatitis C infection" 4270: 4229: 4188: 4139: 4101: 4060: 4011: 3962: 3908: 3854: 3803: 3774: 3750: 3684: 3680: 3649: 3608: 3557: 3514: 3479: 3474: 3439: 3420: 3371: 3330: 3278: 3240: 3226: 3184: 3148: 3113: 3056: 3000: 2943: 2908: 2848: 2809: 2771: 2722: 2662: 2613: 2578: 2529: 2471: 2420: 2393: 2344: 2306: 2265: 2206: 2152: 1951: 1425: 1406: 1267: 1243: 672: 605: 574: 476: 355: 245: 188: 134: 42: 6092: 5835:

Gray PW, Goeddel DV (August 1982). "Structure of the human immune interferon gene".

5821: 3696: 3593: 3406: 2955: 2860: 2625: 2364:"Induction and function of type I and III interferon in response to viral infection" 1311: 1124:, an enzyme that increases protein synthesis and cell proliferation; phosphorylates 418: 277: 74: 9037: 8966: 8961: 8849: 8506: 8348: 8269: 8137: 7826: 7660: 7025: 6228: 6210: 6173: 6163: 6136: 6116: 6072: 6012: 6002: 5923: 5903: 5872: 5852: 5801: 5756: 5746: 5697: 5687: 5640: 5597: 5561: 5516: 5472: 5431: 5404: 5384: 5353: 5333: 5288: 5280: 5239: 5229: 5124: 5074: 4994: 4986: 4945: 4937: 4898: 4834: 4824: 4745: 4735: 4694: 4690: 4686: 4654: 4634: 4588: 4580: 4527: 4517: 4476: 4435: 4427: 4386: 4378: 4337: 4327: 4260: 4219: 4178: 4151: 4131: 4091: 4050: 4042: 4001: 3993: 3952: 3944: 3898: 3890: 3844: 3836: 3793: 3783: 3740: 3730: 3676: 3644: 3639: 3598: 3588: 3549: 3526: 3506: 3469: 3459: 3410: 3402: 3361: 3320: 3312: 3274: 3270: 3230: 3222: 3176: 3140: 3103: 3095: 3068: 3046: 2990: 2982: 2935: 2898: 2890: 2840: 2801: 2761: 2753: 2712: 2674: 2652: 2605: 2568: 2560: 2519: 2511: 2461: 2451: 2383: 2375: 2336: 2296: 2255: 2245: 2198: 2164: 2144: 1919: 1890:—noticed inhibition of viral growth in an area of rabbit-skin or testis previously 1832: 1228: 974: 894: 889:

cells. Such suppression causes a decrease in tumor angiogenesis, a decrease in its

874:, among others) that signal to and co-ordinate the activity of other immune cells. 863: 859: 855: 812: 736: 653: 523: 464: 343: 240: 176: 5505:"The isolation and amino acid/sugar composition of human fibroblastoid interferon" 5181:[Immunizing property of vaccinia virus inactivated by ultraviolets rays]. 5057:

Isaacs A, Lindenmann J (September 1957). "Virus interference. I. The interferon".

2986: 2234:"Innate Immune Antagonism of Mosquito-Borne Flaviviruses in Humans and Mosquitoes" 2218: 2114: 16:

Signaling proteins released by host cells in response to the presence of pathogens

9501: 9415: 9392: 8937: 8854: 8617: 7875: 7561: 7258: 7154: 6939: 6912: 6590: 6352: 6306: 6302: 5940:, Tan YH, Hong WJ, "Gene expression in mammalian cells.", issued 2001 3735: 3553: 2379: 1856: 1512: 1417: 1178: 1158: 1121: 1033: 816: 665: 609: 430: 289: 86: 6889: 6214: 1262:

during the first ten days of viral infection. In the early stages of infection,

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