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62-442: Coxsackieviruses are among the leading causes of aseptic meningitis (the other usual suspects being echovirus and mumps virus ). The entry of coxsackievirus into cells, especially endothelial cells, is mediated by coxsackievirus and adenovirus receptor . Coxsackieviruses are divided into group A and group B viruses based on early observations of their pathogenicity in neonatal mice. Group A coxsackieviruses were noted to cause

124-708: A flaccid paralysis (which was caused by generalized myositis ) while group B coxsackieviruses were noted to cause a spastic paralysis (due to focal muscle injury and degeneration of neuronal tissue). At least 23 serotypes (1–22, 24) of group A and six serotypes (1–6) of group B are recognized. In general, group A coxsackieviruses tend to infect the skin and mucous membranes, causing herpangina ; acute hemorrhagic conjunctivitis ; and hand, foot, and mouth disease . Both group A and group B coxsackieviruses can cause nonspecific febrile illnesses, rashes , upper respiratory tract disease , and aseptic meningitis. The basic reproduction number (R0) for Coxsackievirus A16 (Cox A16)

186-445: A cure for poliomyelitis . Earlier work Dalldorf had done in monkeys suggested that fluid collected from a nonpolio virus preparation could protect against the crippling effects of polio. Using newborn mice as a vehicle, Dalldorf attempted to isolate such protective viruses from the feces of polio patients. In carrying out these experiments, he discovered viruses that often mimicked mild or nonparalytic polio. The virus family he discovered

248-403: A group of signaling proteins made and released by host cells in response to the presence of several viruses . In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses. IFNs belong to the large class of proteins known as cytokines , molecules used for communication between cells to trigger the protective defenses of

310-452: A host animal. Other researchers found this interference can be mediated by a substance produced by the host animal, a protein now known as interferon . Interferon has since become prominent in the treatment of a variety of cancers and infectious diseases. In 2007, an outbreak of coxsackievirus occurred in eastern China. It has been reported that 22 children died. More than 800 people were affected, with 200 children hospitalized. Cavatak ,

372-443: A lack of infection . On the contrary, many cases of aseptic meningitis represent infection with viruses or mycobacteria that cannot be detected with routine methods. Medical professionals will take into consideration the season of the year, the medical history of the individual and family, physical examination, and laboratory results when diagnosing aseptic meningitis. One common medical test used when diagnosing aseptic meningitis

434-457: A mediator of interferon-induced suppression of viral protein translation, although mechanisms of acquired and intrinsic resistance to interferon therapy in HCV are polyfactorial. Coronaviruses evade innate immunity during the first ten days of viral infection. In the early stages of infection, SARS-CoV-2 induces an even lower interferon type I (IFN-I) response than SARS-CoV , which itself

496-424: A multiple organ failure can also signal aseptic meningitis and oftentimes, in babies, seizures and focal neurological deficits can be early symptoms of aseptic meningitis. In fact, in newborns, the mortality rate is 70%. The next set of age group, like children, have similar but varying symptoms of sore throat, rashes, and diarrhea. In adults, symptoms and the harshness of them tend to be less in duration. Additionally,

558-614: A result, an IFN-stimulated gene factor 3 (ISGF3) complex forms—this contains STAT1, STAT2 and a third transcription factor called IRF9 —and moves into the cell nucleus . Inside the nucleus, the ISGF3 complex binds to specific nucleotide sequences called IFN-stimulated response elements (ISREs) in the promoters of certain genes , known as IFN stimulated genes ISGs . 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

620-466: 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 with interferon-α, ribavirin and protease inhibitors such as telaprevir , boceprevir or the nucleotide analog polymerase inhibitor sofosbuvir . Biopsies of patients given the treatment show reductions in liver damage and cirrhosis . Control of chronic hepatitis C by IFN

682-494: 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 interferon . The findings of Isaacs and Lindenmann have been widely confirmed and corroborated in

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744-487: A type of eye infection. There is no clear evidence to suggest that removing the infected tissue ( debridement ) 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. When used in systemic therapy, IFNs are mostly administered by an intramuscular injection. The injection of IFNs in

806-415: A wild-type Coxsackievirus A21, is being used in human clinical trials as an oncolytic virus . SCAR-Fc (Soluble Receptor Analogue) is an experimental prophylactic treatment against coxsackievirus B3 (CVB) infections. Aseptic meningitis Aseptic meningitis is the inflammation of the meninges , a membrane covering the brain and spinal cord , in patients whose cerebral spinal fluid test result

868-695: Is a viral infection, specifically by enteroviruses . In fact, 90 percent of all meningitis cases that are viral are caused by enteroviruses. Other viruses that may cause aseptic meningitis are varicella zoster virus , herpes , and mumps. Other causes may include mycobacteria, fungi, spirochetes, and complications from HIV. Side effects of certain drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (e.g., trimethoprim-sulfamethoxazole or amoxicillin ), and antiepileptic drugs can also cause aseptic meningitis. There are multiple types of aseptic meningitis that are differentiated based on their cause. The term aseptic can be misleading, implying

930-469: Is a weak IFN-I inducer in human cells. SARS-CoV-2 limits the IFN-III response as well. Reduced numbers of plasmacytoid dendritic cells with age is associated with increased COVID-19 severity, possibly because these cells are substantial interferon producers. Ten percent of patients with life-threatening COVID-19 have autoantibodies against type I interferon. Delayed IFN-I response contributes to

992-399: Is also induced by mitogens . Other cytokines, such as interleukin 1 , interleukin 2 , interleukin-12 , tumor necrosis factor and colony-stimulating factor , can also enhance interferon production. By interacting with their specific receptors, IFNs activate signal transducer and activator of transcription ( STAT ) complexes; STATs are a family of transcription factors that regulate

1054-612: Is also linked to its protective role against certain cancers. Another function of interferons is to up-regulate major histocompatibility complex molecules, MHC I and MHC II , and increase immunoproteasome activity. All interferons significantly enhance the presentation of MHC I dependent antigens. Interferon gamma (IFN-gamma) 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 cytotoxic T cells , while

1116-510: Is also regulated by both type I and type II IFNs. PI3K activates P70-S6 Kinase 1 , an enzyme that increases protein synthesis and cell proliferation; phosphorylates ribosomal protein s6 , which is involved in protein synthesis; and phosphorylates a translational repressor protein called eukaryotic translation-initiation factor 4E-binding protein 1 ( EIF4EBP1 ) in order to deactivate it. Interferons can disrupt signaling by other stimuli. For example, interferon alpha induces RIG-G, which disrupts

1178-681: Is associated with reduced hepatocellular carcinoma . A single nucleotide polymorphism (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. Unconfirmed results suggested that interferon eye drops may be an effective treatment for people who have herpes simplex virus epithelial keratitis ,

1240-461: Is available on Interferome , a curated online database of ISGs ( www.interferome.org ); Additionally, STAT homodimers or heterodimers form from different combinations of STAT-1, -3, -4, -5, or -6 during IFN signaling; these dimers 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

1302-621: Is currently being studied further. Sjögren syndrome is also being studied in connection with coxsackievirus, as of January 2010. There were 29 species of coxsackieviruses until 1999, when two of them were abolished and the rest merged into other species. The coxsackieviruses were discovered in 1948–49 by Gilbert Dalldorf, a scientist working at the New York State Department of Health in Albany, New York . Dalldorf, in collaboration with Grace Sickles, had been searching for

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1364-502: Is induced by cytokines such as IL-12, and its expression is restricted to immune cells such as T cells and NK cells . 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 virus-infected cell releases viral particles that can infect nearby cells. However,

1426-458: Is lumbar puncture. A medical professional inserts a needle between two vertebrae to remove cerebrospinal fluid (CSF) from the spinal cord. The cerebrospinal fluid collected from the lumbar puncture is analyzed by microscope examination or by culture to distinguish between bacterial and aseptic meningitis. Samples of CSF undergo cell count, Gram stains, and viral cultures, and polymerase chain reaction (PCR). Polymerase chain reaction has increased

1488-595: Is necessary for conventional interferon-alpha. When used with the antiviral drug ribavirin , PEGylated interferon is effective in treatment of hepatitis C ; 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 protease inhibitors such as boceprevir and telaprevir . There are also interferon-inducing drugs, notably tilorone that

1550-421: Is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses , mycobacteria , spirochetes , fungi , medications , and cancer malignancies. The testing for both meningitis and aseptic meningitis is mostly the same. A cerebrospinal fluid sample is taken by lumbar puncture and is tested for leukocyte levels to determine if there is an infection and goes on to further testing to see what

1612-563: Is shown to be effective against Ebola virus . Interferons were first described in 1957 by Alick Isaacs and Jean Lindenmann at the National Institute for Medical Research in London; the discovery was a result of their studies of viral interference . 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

1674-523: Is used (in combination with chemotherapy and radiation) as a treatment for some cancers. This treatment can be used in hematological malignancy , such as in leukemia and lymphomas including hairy cell leukemia , chronic myeloid leukemia , nodular lymphoma, and cutaneous T-cell lymphoma . Patients with recurrent melanomas receive recombinant IFN-α2b. Both hepatitis B and hepatitis C can be treated with IFN-α, often in combination with other antiviral drugs. Some of those treated with interferon have

1736-588: The immune system that help eradicate pathogens. Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infections . 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 immune cells , such as natural killer cells and macrophages , and they increase host defenses by up-regulating antigen presentation by virtue of increasing

1798-782: The large T antigen of Polyomavirus , the E7 protein of Human papillomavirus (HPV), and the B18R protein of vaccinia virus . Reducing IFN-α activity may prevent signaling via STAT1 , STAT2 , or IRF9 (as with JEV infection) or through the JAK-STAT pathway (as with DEN-2 infection). Several poxviruses 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 double-stranded RNA (dsRNA) to prevent

1860-533: The CSN5-containing COP9 signalosome (CSN), a highly conserved multiprotein complex implicated in protein deneddylation, deubiquitination, and phosphorylation. RIG-G has shown the capacity to inhibit NF-κB and STAT3 signaling in lung cancer cells, which demonstrates the potential of type I IFNs. Many viruses have evolved mechanisms to resist interferon activity. They circumvent the IFN response by blocking downstream signaling events that occur after

1922-520: The Finnish Blood Bank. Large amounts of human beta interferon were made by superinducing the beta interferon gene in human fibroblast cells. 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 RNA

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1984-606: The ability of clinicians to detect viruses such as enterovirus , cytomegalovirus , and herpes virus in the CSF, but many viruses can still escape detection. Other laboratory tests include blood, urine, and stool collection. Medical professionals also have the option of performing a computed tomographic (CT) scan or magnetic resonance imaging (MRI), these tests help observe calcifications or abscesses. If CSF levels are irregular among individuals, they will undergo hospitalization where they receive antiviral therapy. If aseptic meningitis

2046-427: The activity of RNA-dependent protein kinases ; this is the mechanism reovirus 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 protein kinase R , for example, can be disrupted in cells infected with JEV. Some viruses escape

2108-463: The actual cause is. The symptoms are the same for both meningitis and aseptic meningitis but the severity of the symptoms and the treatment can depend on the certain cause. The most common cause of aseptic meningitis is by viral infection. Other causes may include side-effects from drugs and connective tissue disorders. Aseptic meningitis is a disease that can depend on the patient's age, however, research has shown some distinct symptoms that indicate

2170-591: The anti-viral activities of interferons by gene (and thus protein) mutation. The H5N1 influenza virus, also known as bird flu, has resistance to interferon and other anti-viral cytokines that is attributed to a single amino acid change in its Non-Structural Protein 1 (NS1), although the precise mechanism of how this confers immunity is unclear. The relative resistance of hepatitis C virus genotype I to interferon-based therapy has been attributed in part to homology between viral envelope protein E2 and host protein kinase R,

2232-616: The cell. Another cellular enzyme, RNAse L —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 p53 activity, which kills virus-infected cells by promoting apoptosis . The effect of IFN on p53

2294-426: The coxsackieviruses stimulated many virologists to use this system, and ultimately resulted in the isolation of a large number of so-called "enteric" viruses from the gastrointestinal tract that were unrelated to poliovirus, and some of which were oncogenic (cancer-causing). The discovery of the coxsackieviruses yielded further evidence that viruses can sometimes interfere with each other's growth and replication within

2356-548: The cytokine binds to its receptor, by preventing further IFN production, and by inhibiting the functions of proteins that are induced by IFN. Viruses that inhibit IFN signaling include Japanese Encephalitis Virus (JEV), dengue type 2 virus (DEN-2), and viruses of the herpesvirus family, such as human cytomegalovirus (HCMV) and Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8). Viral proteins proven to affect IFN signaling include EBV nuclear antigen 1 (EBNA1) and EBV nuclear antigen 2 (EBNA-2) from Epstein-Barr virus ,

2418-632: The cytoplasmic receptors RIG-I or MDA5 , can trigger release of IFNs. Toll Like Receptor 3 ( TLR3 ) is important for inducing interferons in response to the presence of double-stranded RNA viruses ; the ligand for this receptor is double-stranded RNA (dsRNA) . After binding dsRNA, this receptor activates the transcription factors IRF3 and NF-κB , which are important for initiating synthesis of many inflammatory proteins. RNA interference 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)

2480-508: The expression of major histocompatibility complex (MHC) antigens . Certain symptoms of infections, such as fever , muscle pain and "flu-like symptoms", are also caused by the production of IFNs and other cytokines . 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 viral infections and for

2542-458: 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. STAT activation initiates the most well-defined cell signaling pathway for all IFNs, the classical Janus kinase -STAT ( JAK-STAT ) signaling pathway. In this pathway, JAKs associate with IFN receptors and, following receptor engagement with IFN, phosphorylate both STAT1 and STAT2 . As

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2604-437: 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

2666-594: 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 helper T cells ; these cells release cytokines (such as more interferons and interleukins , among others) that signal to and co-ordinate the activity of other immune cells. Interferons can also suppress angiogenesis by down regulation of angiogenic stimuli deriving from tumor cells. They also suppress

2728-439: 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 enzyme known as protein kinase R (PKR). This enzyme phosphorylates a protein known as eIF-2 in response to new viral infections; the phosphorylated eIF-2 forms an inactive complex with another protein, called eIF2B , to reduce protein synthesis within

2790-464: 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

2852-651: The literature. 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 vaccine for smallpox , Yasu-ichi Nagano and Yasuhiko Kojima—two Japanese virologists working at the Institute for Infectious Diseases at the University of Tokyo —noticed inhibition of viral growth in an area of rabbit-skin or testis previously inoculated with UV-inactivated virus. They hypothesised that some "viral inhibitory factor"

2914-424: The mice, with extensive skeletal muscle necrosis; Coxsackie B causes less severe infection in the mice, but with damage to more organ systems, such as heart, brain, liver, pancreas, and skeletal muscles.) The use of suckling mice was not Dalldorf's idea but was brought to his attention in a paper written by Danish scientists Orskov and Andersen in 1947, who were using such mice to study a mouse virus. The discovery of

2976-546: The muscle or under the skin is generally well tolerated. 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 at the site of injection are also frequently observed. IFN therapy causes immunosuppression , in particular through neutropenia and can result in some infections manifesting in unusual ways. Several different types of interferons are approved for use in humans. One

3038-754: The pathogenic inflammation ( cytokine storm ) seen in later stages of COVID-19 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. With pegylated IFN lambda, the relative risk for hospitalization with the Omicron strains is reduced by about 80 %. Interferon beta-1a and interferon beta-1b are used to treat and control multiple sclerosis , an autoimmune disorder . This treatment may help in reducing attacks in relapsing-remitting multiple sclerosis and slowing disease progression and activity in secondary progressive multiple sclerosis. Interferon therapy

3100-403: The possibility of aseptic meningitis. A variety of patients notice a change in body temperatures (higher than normal temperatures 38-40 °C), marked with the possibility of vomiting, headaches, firm neck pain, and even lack of appetite . In younger patients, like babies, a meningeal inflammation can be noticed along with the possibility of hepatic necrosis and myocarditis . In serious cases,

3162-769: The presence of a GAS element. 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 adaptor proteins called CRKL , a nuclear adaptor for STAT5 that also regulates signaling through the C3G / Rap1 pathway. Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription. Antiviral and antiproliferative effects specific to type I IFNs result from p38 MAP kinase signaling. The phosphatidylinositol 3-kinase (PI3K) signaling pathway

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3224-434: The probability of developing aseptic meningitis increases when patients have a case of mumps or herpes. Symptoms of meningitis caused by an acute viral infection last between one and two weeks. When aseptic meningitis is caused by cytomegalovirus 20 percent of individuals face mortality or morbidity. If left untreated it can affect an individual's hearing and learning abilities. The most common cause of aseptic meningitis

3286-666: The proliferation of endothelial cells. Such suppression causes a decrease in tumor angiogenesis, a decrease in its vascularization and subsequent growth inhibition. Interferons, such as interferon gamma , directly activate other immune cells, such as macrophages and natural killer cells . 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 glycoproteins , viral RNA , bacterial endotoxin (lipopolysaccharide), bacterial flagella , CpG motifs —by pattern recognition receptors , such as membrane bound toll like receptors or

3348-476: The regulation of the immune system. Based on the type of receptor through which they signal, human interferons have been classified into three major types. 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 interferon

3410-551: Was caused by herpes simplex virus (HSV), the individual will receive acyclovir, an antiviral drug. Aseptic meningitis was first described by Wallgren in 1925. Aseptic meningitis cases have varied historically. Aseptic meningitis caused by mumps has declined in the United States due to the increased use of vaccination which prevents mumps cases from occurring. Interferon Interferons ( IFN s, / ˌ ɪ n t ər ˈ f ɪər ɒ n / IN -tər- FEER -on ) are

3472-466: Was encoded by a family of many related genes. The type II IFN (IFN-γ) gene was also isolated around this time. Interferon was first synthesized manually at Rockefeller University in the lab of Dr. Bruce Merrifield , using solid phase peptide synthesis , one amino acid at a time. He later won the Nobel Prize in chemistry. Interferon was scarce and expensive until 1980, when the interferon gene

3534-550: Was estimated to a median of 2.50 with an interquartile range of 1.96 to 3.67. Group B coxsackieviruses tend to infect the heart, pleura, pancreas, and liver, causing pleurodynia , myocarditis , pericarditis , and hepatitis (inflammation of the liver not related to the hepatotropic viruses ). Coxsackie B infection of the heart can lead to pericardial effusion . The development of insulin-dependent diabetes has recently been associated with recent enteroviral infection, particularly coxsackievirus B pancreatitis . This relationship

3596-546: Was eventually given the name Coxsackie, from Coxsackie, New York , a small town on the Hudson River where Dalldorf had obtained the first fecal specimens. Dalldorf also collaborated with Gifford on many early papers. The coxsackieviruses subsequently were found to cause a variety of infections, including epidemic pleurodynia ( Bornholm disease ), and were subdivided into groups A and B based on their pathology in newborn mice. (Coxsackie A virus causes paralysis and death of

3658-751: Was first approved for medical use in 1986. For example, in January 2001, the Food and Drug Administration (FDA) approved the use of PEGylated interferon-alpha in the USA; in this formulation, PEGylated interferon-alpha-2b ( Pegintron ), polyethylene glycol is linked to the interferon molecule to make the interferon last longer in the body. Approval for PEGylated interferon-alpha-2a ( Pegasys ) followed in October 2002. These PEGylated drugs are injected once weekly, rather than administering two or three times per week, as

3720-442: Was inserted into bacteria using recombinant DNA technology , allowing mass cultivation and purification from bacterial cultures or derived from yeasts . 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

3782-417: Was not reported until 1978. A series of publications from the laboratories of Sidney Pestka 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 confirmed that IFN-α

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3844-564: Was present in the tissues infected with virus and attempted to isolate and characterize this factor from tissue homogenates . Independently, Monto Ho, in John Enders '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 viral inhibitory factor (VIF). It took another fifteen to twenty years, using somatic cell genetics, to show that

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