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71-420: 1EKU , 1FG9 , 1FYH , 1HIG , 3BES 3458 15978 ENSG00000111537 ENSMUSG00000055170 P01579 P01580 NM_000619 NM_008337 NP_000610 NP_032363 Interferon gamma ( IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons . The existence of this interferon, which early in its history was known as immune interferon,

142-424: A GTPase that inhibits chlamydial proliferation. In both the human and rodent systems, chlamydia has evolved mechanisms to circumvent the negative effects of host cell behavior. There is evidence that interferon-gamma expression is regulated by a pseudoknotted element in its 5' UTR . There is also evidence that interferon-gamma is regulated either directly or indirectly by the microRNAs : miR-29. Furthermore, there

213-502: A positive feedback loop —while suppressing T h 2 cell differentiation. (Equivalent defining cytokines for other cells include IL-4 for T h 2 cells and IL-17 for Th17 cells .) NK cells and CD8+ cytotoxic T cells also produce IFNG. IFNG suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK - RANKL signaling pathway, which otherwise stimulates

284-426: A competent virus is formed. This typically involves capsid modifications that are provided enzymes (host or virus-encoded). The final step in viral replication is release, which is when the newly assembled and mature viruses leave the host cell. How a virus releases from the host cell is dependent on the type of virus it is. One common type of release is budding. This occurs when viruses that form their envelope from

355-613: A history of spontaneous miscarriage, when compared to women with no history of spontaneous miscarriage. Additionally, low-IFNG levels are associated with women who successfully carry to term. It is possible that IFNG is cytotoxic to trophoblasts , which leads to miscarriage. However, causal research on the relationship between IFNG and miscarriage has not been performed due to ethical constraints . Recombinant human IFNG, as an expensive biopharmaceutical, has been expressed in different expression systems including prokaryotic, protozoan, fungal (yeasts), plant, insect and mammalian cells. Human IFNG

426-586: A protein heterodimer is formed by two different proteins. Most protein dimers in biochemistry are not connected by covalent bonds . An example of a non-covalent heterodimer is the enzyme reverse transcriptase , which is composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein NEMO . Some proteins contain specialized domains to ensure dimerization (dimerization domains) and specificity. The G protein-coupled cannabinoid receptors have

497-449: A role in seborrheic dermatitis. IFNG has a significant anti-viral effect in herpes simplex virus I (HSV) infection. IFNG compromises the microtubules that HSV relies upon for transport into an infected cell's nucleus, inhibiting the ability of HSV to replicate. Studies in mice on acyclovir resistant herpes have shown that IFNG treatment can significantly reduce herpes viral load. The mechanism by which IFNG inhibits herpes reproduction

568-522: Is a cytokine, meaning it functions by signaling to other cells in the immune system and influencing their immune response. There are many immune cells type II IFN acts on. Some of its main functions are to induce IgG isotype switching in B cells ; upregulate major histocompatibility complex (MHC) class II expression on APCs ; induce CD8 cytotoxic T cell differentiation, activation, and proliferation; and activate macrophages . In macrophages, type II IFN stimulates IL-12 expression. IL-12 in turn promotes

639-654: Is also one of the most-studied types of viruses, alongside the double-stranded DNA viruses. The positive-sense RNA viruses and indeed all genes defined as positive-sense can be directly accessed by host ribosomes to immediately form proteins. These can be divided into two groups, both of which replicate in the cytoplasm: Examples of this class include the families Coronaviridae , Flaviviridae , and Picornaviridae . The negative-sense RNA viruses and indeed all genes defined as negative-sense cannot be directly accessed by host ribosomes to immediately form proteins. Instead, they must be transcribed by viral polymerases into

710-429: Is an important activator of macrophages and inducer of major histocompatibility complex class II molecule expression. Aberrant IFNG expression is associated with a number of autoinflammatory and autoimmune diseases . The importance of IFNG in the immune system stems in part from its ability to inhibit viral replication directly, and most importantly from its immunostimulatory and immunomodulatory effects. IFNG

781-640: Is approved by the U.S. Food and Drug Administration to treat chronic granulomatous disease (CGD) and osteopetrosis . The mechanism by which IFNG benefits CGD is via enhancing the efficacy of neutrophils against catalase-positive bacteria by correcting patients' oxidative metabolism. It was not approved to treat idiopathic pulmonary fibrosis (IPF). In 2002, the manufacturer InterMune issued a press release saying that phase III data demonstrated survival benefit in IPF and reduced mortality by 70% in patients with mild to moderate disease. The U.S. Department of Justice charged that

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852-474: Is commonly expressed in Escherichia coli , marketed as ACTIMMUNE®, however, the resulting product of the prokaryotic expression system is not glycosylated with a short half-life in the bloodstream after injection; the purification process from bacterial expression system is also very costly. Other expression systems like Pichia pastoris did not show satisfactory results in terms of yields. Interferon gamma 1b

923-413: Is defined by the removal of the virion's protein "coat" and the release of its genetic material. This step occurs in the same area that viral transcription occurs. Different viruses have various mechanisms for uncoating. Some RNA viruses such as Rhinoviruses use the low pH in a host cell's endosomes to activate their uncoating mechanism. This involves the rhinovirus releasing a protein that creates holes in

994-529: Is evidence that interferon-gamma expression is regulated via GAPDH in T-cells. This interaction takes place in the 3'UTR, where binding of GAPDH prevents the translation of the mRNA sequence. This article incorporates text from the United States National Library of Medicine , which is in the public domain . Protein dimer A protein homodimer is formed by two identical proteins while

1065-399: Is independent of T-cells, which means that IFNG may be an effective treatment in individuals with low T-cells. Chlamydia infection is impacted by IFNG in host cells. In human epithelial cells, IFNG upregulates expression of indoleamine 2,3-dioxygenase , which in turn depletes tryptophan in hosts and impedes chlamydia's reproduction. Additionally, in rodent epithelial cells, IFNG upregulates

1136-937: Is part of the class II cytokine receptor family. The IFNGR is composed of two subunits: the IFNGR1 and IFNGR2 . IFNGR1 is associated with JAK1 and IFNGR2 is associated with JAK2 . Upon IFNG binding the receptor, IFNGR1 and IFNGR2 undergo conformational changes that result in the autophosphorylation and activation of JAK1 and JAK2. This leads to a signaling cascade and eventual transcription of target genes. The expression of 236 different genes has been linked to type II IFN-mediated signaling. The proteins expressed by type II IFN-mediated signaling are primarily involved in promoting inflammatory immune responses and regulating other cell-mediated immune responses, such as apoptosis , intracellular IgG trafficking, cytokine signaling and production, hematopoiesis , and cell proliferation and differentiation . One key pathway triggered by IFNG binding IFNGRs

1207-427: Is primarily secreted by CD4 T helper 1 (Th1) cells, natural killer (NK) cells, and CD8 cytotoxic T cells . The expression of type II IFN is upregulated and downregulated by cytokines. By activating signaling pathways in cells such as macrophages , B cells , and CD8 cytotoxic T cells , it is able to promote inflammation, antiviral or antibacterial activity, and cell proliferation and differentiation . Type II IFN

1278-403: Is produced predominantly by natural killer cells (NK) and natural killer T cells (NKT) as part of the innate immune response, and by CD4 Th1 and CD8 cytotoxic T lymphocyte ( CTL ) effector T cells once antigen -specific immunity develops as part of the adaptive immune response. IFNG is also produced by non-cytotoxic innate lymphoid cells (ILC), a family of immune cells first discovered in

1349-408: Is secreted by T helper cells (specifically, T h 1 cells), cytotoxic T cells (T C cells), macrophages, mucosal epithelial cells and NK cells . IFNG is both an important autocrine signal for professional APCs in early innate immune response, and an important paracrine signal in adaptive immune response. The expression of IFNG is induced by the cytokines IL-12, IL-15, IL-18, and type I IFN. IFNG

1420-426: Is serologically different from interferon type 1 , binds to different receptors, and is encoded by a separate chromosomal locus. Type II IFN has played a role in the development of cancer immunotherapy treatments due to its ability to prevent tumor growth. IFNG, or type II interferon, is a cytokine that is critical for innate and adaptive immunity against viral , some bacterial and protozoan infections . IFNG

1491-684: Is the Janus Kinase and Signal Transducer and Activator of Transcription pathway, more commonly referred to as the JAK-STAT pathway . In the JAK-STAT pathway, activated JAK1 and JAK2 proteins regulate the phosphorylation of tyrosine in STAT1 transcription factors. The tyrosines are phosphorylated at a very specific location, allowing activated STAT1 proteins to interact with each other come together to form STAT1-STAT1 homodimers . The STAT1-STAT1 homodimers can then enter

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1562-424: Is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in

1633-552: Is the only Type II interferon and it is serologically distinct from Type I interferons; it is acid-labile, while the type I variants are acid-stable. IFNG has antiviral, immunoregulatory, and anti-tumor properties. It alters transcription in up to 30 genes producing a variety of physiological and cellular responses. Among the effects are: IFNG is the primary cytokine that defines T h 1 cells: T h 1 cells secrete IFNG, which in turn causes more undifferentiated CD4 cells (Th0 cells) to differentiate into T h 1 cells, representing

1704-415: Is to trigger an immune response by the patient's immune cells to attack and kill malignant (cancer-causing) tumor cells. Type II IFN deficiency has been linked to several types of cancer, including B-cell lymphoma and lung cancer. Furthermore, it has been found that in patients receiving the drug durvalumab to treat non-small cell lung carcinoma and transitional cell carcinoma had higher response rates to

1775-685: The Circoviridae and Parvoviridae . They replicate within the nucleus, and form a double-stranded DNA intermediate during replication. A human Anellovirus called TTV is included within this classification and is found in almost all humans, infecting them asymptomatically in nearly every major organ . RNA viruses: The polymerase of RNA viruses lacks the proofreading functions found in the polymerase of DNA viruses. This contributed to RNA viruses having lower replicative fidelity compared to DNA viruses, causing RNA viruses to be highly mutagenic, which can increase their overall survival rate. RNA viruses lack

1846-449: The Food and Drug Administration (FDA) to treat cancer, except for malignant osteoporosis . This is most likely due to the fact that while type II IFN is involved in antitumor immunity, some of its functions may enhance the progression of a cancer. When type II IFN acts on tumor cells, it may induce the expression of a transmembrane protein known as programmed death-ligand 1 ( PDL1 ), which allows

1917-505: The Reoviridae and Birnaviridae . Replication is monocistronic and includes individual, segmented genomes, meaning that each of the genes codes for only one protein, unlike other viruses, which exhibit more complex translation. These viruses consist of two types, however both share the fact that replication is primarily in the cytoplasm, and that replication is not as dependent on the cell cycle as that of DNA viruses. This class of viruses

1988-482: The glycosaminoglycan heparan sulfate (HS) at the cell surface. However, in contrast to many other heparan sulfate binding proteins, where binding promotes biological activity , the binding of IFNG to HS inhibits its biological activity. The structural models shown in figures 1-3 for IFNG are all shortened at their C-termini by 17 amino acids. Full length IFNG is 143 amino acids long, the models are 126 amino acids long. Affinity for heparan sulfate resides solely within

2059-459: The rhinovirus uses their virus attachment protein to bind to the receptor ICAM-1 on host cells that is normally used to facilitate adhesion between other host cells. Entry, or penetration, is the second step in viral replication. This step is characterized by the virus passing through the plasma membrane of the host cell. The most common way a virus gains entry to the host cell is by receptor-mediated endocytosis , which comes at no energy cost to

2130-449: The "readable" complementary positive-sense. These can also be divided into two groups: Examples in this class include the families Orthomyxoviridae , Paramyxoviridae , Bunyaviridae , Filoviridae , and Rhabdoviridae (which includes rabies ). A well-studied family of this class of viruses include the retroviruses . One defining feature is the use of reverse transcriptase to convert the positive-sense RNA into DNA. Instead of using

2201-504: The RNA for templates of proteins, they use DNA to create the templates, which is spliced into the host genome using integrase . Replication can then commence with the help of the host cell's polymerases. This small group of viruses, exemplified by the Hepatitis B virus, have a double-stranded, gapped genome that is subsequently filled in to form a covalently closed circle ( cccDNA ) that serves as

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2272-467: The RNA is in a replicative form. Viruses may undergo two types of life cycles: the lytic cycle and the lysogenic cycle. In the lytic cycle, the virus introduces its genome into a host cell and initiates replication by hijacking the host's cellular machinery to make new copies of the virus. In the lysogenic life cycle, the viral genome is incorporated into the host genome. The host genome will undergo its normal life cycle, replicating and dividing replicating

2343-749: The T h 1 helper cells and become fibroblast-like cells walling off the infection. Uterine natural killer cells (NKs) secrete high levels of chemoattractants , such as IFNG in mice. IFNG dilates and thins the walls of maternal spiral arteries to enhance blood flow to the implantation site . This remodeling aids in the development of the placenta as it invades the uterus in its quest for nutrients. IFNG knockout mice fail to initiate normal pregnancy-induced modification of decidual arteries. These models display abnormally low amounts of cells or necrosis of decidua. In humans, elevated levels of IFN gamma have been associated with increased risk of miscarriage. Correlation studies have observed high IFNG levels in women with

2414-431: The ability to form both homo- and heterodimers with several types of receptors such as mu-opioid , dopamine and adenosine A2 receptors. E. coli alkaline phosphatase , a dimer enzyme, exhibits intragenic complementation . That is, when particular mutant versions of alkaline phosphatase were combined, the heterodimeric enzymes formed as a result exhibited a higher level of activity than would be expected based on

2485-610: The activation of protein kinase C delta type ( PKC-δ ) which phosphorylates the amino acid serine in STAT1 transcription factors. The phosphorylation of the serine in STAT1-STAT1 homodimers are essential for the full transcription process to occur. Other signaling pathways that are triggered by IFNG are the mTOR signaling pathway , the MAPK signaling pathway , and the PI3K/AKT signaling pathway . IFNG

2556-564: The basic observation underlying the now widely employed interferon gamma release assay used to test for tuberculosis . In humans, the IFNG protein is encoded by the IFNG gene . Through cell signaling, interferon gamma plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by type II IFN is the JAK-STAT signaling pathway . IFNG plays an important role in both innate and adaptive immunity. Type II IFN

2627-423: The capacity to identify and repair mismatched or damaged nucleotides, and thus, RNA genomes are prone to mutations introduced by mechanisms intrinsic and extrinsic to viral replication. RNA viruses present a therapeutic double-edged sword: RNA viruses can withstand the challenge of antiviral drugs, cause epidemics, and infect multiple host species due to their mutagenic nature, making them difficult to treat. However,

2698-423: The cell nucleus. They then initiate transcription by binding to gamma interferon activation site (GAS) elements, which are located in the promoter region of Interferon-stimulated genes (ISGs) that express for antiviral effector proteins, as well as positive and negative regulators of type II IFN signaling pathways. The JAK proteins also lead to the activation of phosphatidylinositol 3-kinase ( PI3K ). PI3K leads to

2769-665: The cell to forcefully undergo cell division , which may lead to transformation of the cell and, ultimately, cancer . An example of a family within this classification is the Adenoviridae . There is only one well-studied example in which a class 1 family of viruses does not replicate within the nucleus. This is the Poxvirus family, which comprises highly pathogenic viruses that infect vertebrates . Viruses that fall under this category include ones that are not as well-studied, but still do pertain highly to vertebrates. Two examples include

2840-414: The corresponding cellular machinery for said genetic material. Viruses that contain double-stranded DNA (dsDNA) share the same kind of genetic material as all organisms, and can therefore use the replication enzymes in the host cell nucleus to replicate the viral genome. Many RNA viruses typically replicate in the cytosol , and can directly access the host cell's ribosomes to manufacture viral proteins once

2911-425: The deactivation of the immune cells involved in the killing of the tumor cells. Type II IFN prevents tumor cell division by directly acting on the tumor cells, which results in increased expression of proteins that inhibit the tumor cells from continuing through the cell cycle (i.e., cell cycle arrest). Type II IFN can also prevent tumor growth by indirectly acting on endothelial cells lining the blood vessels close to

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2982-447: The deleted sequence of 17 amino acids. Within this sequence of 17 amino acids lie two clusters of basic amino acids termed D1 and D2, respectively. Heparan sulfate interacts with both of these clusters. In the absence of heparan sulfate the presence of the D1 sequence increases the rate at which IFNG-receptor complexes form. Interactions between the D1 cluster of amino acids and the receptor may be

3053-471: The drug, and the drug stunted the progression of both types of cancer for a longer duration of time. Thus, promoting the upregulation of type II IFN has been proven to be a crucial part in creating effective cancer immunotherapy treatments. IFNG is not approved yet for the treatment in any cancer immunotherapy . However, improved survival was observed when IFNG was administered to patients with bladder carcinoma and melanoma cancers. The most promising result

3124-628: The early 2010s. The primary cells that secrete type II IFN are CD4 T helper 1 (Th1) cells, natural killer (NK) cells, and CD8 cytotoxic T cells . It can also be secreted by antigen presenting cells ( APCs ) such as dendritic cells ( DCs ), macrophages ( MΦs ), and B cells to a lesser degree. Type II IFN expression is upregulated by the production of interleukin cytokines, such as IL-12 , IL-15 , IL-18 , as well as type I interferons (IFN-α and IFN-β). Meanwhile, IL-4 , IL-10 , transforming growth factor-beta (TGF-β) and glucocorticoids are known to downregulate type II IFN expression. Type II IFN

3195-446: The endosome, and allows the virus to release its genome through the holes. Many DNA viruses travel to the host cells nucleus and release their genetic material through nuclear pores. The fourth step in the viral cycle is replication, which is defined by the rapid production of the viral genome. How a virus undergoes replication relies on the type of genetic material the virus possesses. Based on their genetic material, viruses will hijack

3266-455: The first step in complex formation. By binding to D1 HS may compete with the receptor and prevent active receptor complexes from forming. The biological significance of heparan sulfates interaction with IFNG is unclear; however, binding of the D1 cluster to HS may protect it from proteolytic cleavage . IFNG binds to the type II cell-surface receptor, also known as the IFN gamma receptor (IFNGR) which

3337-495: The host cell and inject its DNA or RNA into the host to initiate infection. Attachment to a host cell is often achieved by a virus attachment protein that extends from the protein shell ( capsid ), of a virus. This protein is responsible for binding to a surface receptor on the plasma membrane (or membrane carbohydrates) of a host cell. Viruses can exploit normal cell receptor functions to allow attachment to occur by mimicking molecules that bind to host cell receptors. For example,

3408-406: The host nucleus before it is able to replicate. Some of these viruses require host cell polymerases to replicate their genome , while others, such as adenoviruses or herpes viruses, encode their own replication factors. However, in either case, replication of the viral genome is highly dependent on a cellular state permissive to DNA replication and, thus, on the cell cycle . The virus may induce

3479-426: The host membrane, and after entry, the virion becomes uncoated, and its genomic material is then transferred into the cytoplasm. Cell-to-cell fusion: Some viruses prompt specific protein expression on the surfaces of infected cells to attract uninfected cells. This interaction causes the uninfected cell to fuse with the infected cell at lower pH levels to form a multinuclear cell known as a syncytium. Endocytic routes:

3550-436: The host's plasma membrane bend the membrane around the capsid. As the virus bends the plasma membrane it begins to wrap around the whole capsid until the virus is no longer attached to the host cell. Another common way viruses leave the host cell is through cell lysis , where the viruses lyse the cell causing it to burst which releases mature viruses that were in the host cell. Viruses are split into seven classes, according to

3621-660: The lung. The infectious pathophysiology of granulomas is discussed primarily here. The key association between IFNG and granulomas is that IFNG activates macrophages so that they become more powerful in killing intracellular organisms. Activation of macrophages by IFNG from T h 1 helper cells in mycobacterial infections allows the macrophages to overcome the inhibition of phagolysosome maturation caused by mycobacteria (to stay alive inside macrophages). The first steps in IFNG-induced granuloma formation are activation of T h 1 helper cells by macrophages releasing IL-1 and IL-12 in

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3692-402: The nucleus while most RNA viruses develop solely in cytoplasm. Viruses multiply only in living cells. The host cell must provide the energy and synthetic machinery and the low-molecular-weight precursors for the synthesis of viral proteins and nucleic acids. Virus replication occurs in seven stages: It is the first step of viral replication. Some viruses attach to the cell membrane of

3763-419: The other steps, how a particular virus is assembled is dependent on what type of virus it is. Assembly can occur in the plasma membrane, cytosol, nucleus, golgi apparatus, and other locations within the host cell. Some viruses only insert their genome into a capsid once the capsid is completed, while in other viruses the will capsid will wrap around the genome as it is being copied. This is the final step before

3834-401: The plasma membrane and can spread within the host via fusion or cell-cell fusion. Viruses attach to proteins on the host cell surface known as cellular receptors or attachment factors to aid entry. Evidence shows that viruses utilize ion channels on the host cells during viral entry. Fusion: External viral proteins promote the fusion of the virion with the plasma membrane. This forms a pore in

3905-421: The presence of intracellular pathogens, and presentation of antigens from those pathogens. Next the T h 1 helper cells aggregate around the macrophages and release IFNG, which activates the macrophages. Further activation of macrophages causes a cycle of further killing of intracellular bacteria, and further presentation of antigens to T h 1 helper cells with further release of IFNG. Finally, macrophages surround

3976-418: The process by which an intracellular vesicle is formed by membrane invagination, which results in the engulfment of extracellular and membrane-bound components, in this context, a virus. Non-endocytic routes: the process by which viral particles are released into the cell by fusion of the extracellular viral envelope and the membrane of the host cell. Uncoating is the third step in viral replication. Uncoating

4047-646: The production of NF-κB . A granuloma is the body's way of dealing with a substance it cannot remove or sterilize. Infectious causes of granulomas (infections are typically the most common cause of granulomas) include tuberculosis , leprosy , histoplasmosis , cryptococcosis , coccidioidomycosis , blastomycosis , and toxoplasmosis. Examples of non-infectious granulomatous diseases are sarcoidosis , Crohn's disease , berylliosis , giant-cell arteritis , granulomatosis with polyangiitis , eosinophilic granulomatosis with polyangiitis , pulmonary rheumatoid nodules , and aspiration of food and other particulate material into

4118-1087: The relative activities of the parental enzymes. These findings indicated that the dimer structure of the E. coli alkaline phosphatase allows cooperative interactions between the constituent mutant monomers that can generate a more functional form of the holoenzyme . The dimer has two active sites, each containing two zinc ions and a magnesium ion.[8] 6. Conn. (2013). G protein coupled receptors modeling, activation, interactions and virtual screening (1st ed.). Academic Press. 7. Matthews, Jacqueline M. Protein Dimerization and Oligomerization in Biology . Springer New York, 2012. 8. Hjorleifsson, Jens Gu[eth]Mundur, and Bjarni Asgeirsson. “Cold-Active Alkaline Phosphatase Is Irreversibly Transformed into an Inactive Dimer by Low Urea Concentrations.” Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics , vol. 1864, no. 7, 2016, pp. 755–765, https://doi.org/10.1016/j.bbapap.2016.03.016. Viral replication Viral replication

4189-463: The release contained false and misleading statements. InterMune's chief executive, Scott Harkonen, was accused of manipulating the trial data, was convicted in 2009 of wire fraud, and was sentenced to fines and community service. Harkonen appealed his conviction to the U.S. Court of Appeals for the Ninth Circuit, and lost. Harkonen was granted a full pardon on January 20, 2021. Preliminary research on

4260-510: The reverse transcriptase protein that often comes with the RNA virus can be used as an indirect target for RNA viruses, preventing transcription and synthesis of viral particles. (This is the basis for anti-AIDs and anti-HIV drugs ) Like most viruses with RNA genomes, double-stranded RNA viruses do not rely on host polymerases for replication to the extent that viruses with DNA genomes do. Double-stranded RNA viruses are not as well-studied as other classes. This class includes two major families,

4331-1132: The role of IFNG in treating Friedreich's ataxia (FA) conducted by Children's Hospital of Philadelphia has found no beneficial effects in short-term (< 6-months) treatment. However, researchers in Turkey have discovered significant improvements in patients' gait and stance after 6 months of treatment. Although not officially approved, Interferon gamma has also been shown to be effective in treating patients with moderate to severe atopic dermatitis . Specifically, recombinant IFNG therapy has shown promise in patients with lowered IFNG expression, such as those with predisposition to herpes simplex virus, and pediatric patients. IFNG increases an anti-proliferative state in cancer cells, while upregulating MHC I and MHC II expression, which increases immunorecognition and removal of pathogenic cells. IFNG also reduces metastasis in tumors by upregulating fibronectin , which negatively impacts tumor architecture. Increased IFNG mRNA levels in tumors at diagnosis has been associated to better responses to immunotherapy. The goal of cancer immunotherapy

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4402-481: The secretion of IFNG by NK cells and Th1 cells, and it signals naive T helper cells (Th0) to differentiate into Th1 cells. The IFNG monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region. This is shown in the structural models below. The α-helices in the core of the structure are numbered 1 to 6. The biologically active dimer is formed by anti-parallel inter-locking of

4473-450: The site of the tumor, cutting off blood flow to the tumor cells and thus the supply of necessary resources for tumor cell survival and proliferation. The importance of type II IFN in cancer immunotherapy has been acknowledged; current research is studying the effects of type II IFN on cancer, both as a solo form of treatment and as a form of treatment to be administered alongside other anticancer drugs. But type II IFN has not been approved by

4544-507: The tumor cells to evade an attack from immune cells. Type II IFN-mediated signaling may also promote angiogenesis (formation of new blood vessels to the tumor site) and tumor cell proliferation. Interferon gamma has been shown to interact with Interferon gamma receptor 1 and Interferon gamma receptor 2 . Interferon gamma has been shown to be a crucial player in the immune response against some intracellular pathogens, including that of Chagas disease . It has also been identified as having

4615-494: The two monomers as shown below. In the cartoon model, one monomer is shown in red, the other in blue. Cellular responses to IFNG are activated through its interaction with a heterodimeric receptor consisting of Interferon gamma receptor 1 (IFNGR1) and Interferon gamma receptor 2 (IFNGR2). IFN-γ binding to the receptor activates the JAK-STAT pathway . Activation of the JAK-STAT pathway induces upregulation of interferon-stimulated genes (ISGs), including MHC II. IFNG also binds to

4686-668: The type of genetic material and method of mRNA production, each of which has its own families of viruses, which in turn have differing replication strategies themselves. David Baltimore , a Nobel Prize -winning biologist, devised a system called the Baltimore Classification System to classify different viruses based on their unique replication strategy. There are seven different replication strategies based on this system (Baltimore Class I, II, III, IV, V, VI, VII). The seven classes of viruses are listed here briefly and in generalities. This type of virus usually must enter

4757-431: The unglycosylated form that is expressed in E. coli . Type II IFN enhances Th1 cell, cytotoxic T cell, and APC activities, which results in an enhanced immune response against the malignant tumor cells, leading to tumor cell apoptosis and necroptosis (cell death). Furthermore, Type II IFN suppresses the activity of regulatory T cells , which are responsible for silencing immune responses against pathogens, preventing

4828-502: The viral genome along with its own. The viral genome can be triggered to begin viral production via chemical and environmental stimulants. Once a lysogenic virus enters the lytic life cycle, it will continue in the viral production pathways and proceed with transcription / mRNA production. (ex: Cold sores, herpes simplex virus (HSV)-1, lysogenic bacteriophages, etc.) Assembly is when the newly manufactured viral proteins and genomes are gathered and put together to form immature viruses. Like

4899-460: The virus, only the host cell. Receptor-mediated endocytosis occurs when a molecule (in this case a virus) binds to receptor on the membrane of the cell. A series of chemical signals from this binding causes the cell to wrap the attached virus in the plasma membrane around it forming a virus-containing vesicle inside the cell. Viruses enter host cells using a variety of mechanisms, including the endocytic and non-endocytic routes. They can also fuse at

4970-667: Was achieved in patients with stage 2 and 3 of ovarian carcinoma . On the contrary, it was stressed: "Interferon-γ secreted by CD8-positive lymphocytes upregulates PD-L1 on ovarian cancer cells and promotes tumour growth." The in vitro study of IFNG in cancer cells is more extensive and results indicate anti-proliferative activity of IFNG leading to the growth inhibition or cell death, generally induced by apoptosis but sometimes by autophagy . In addition, it has been reported that mammalian glycosylation of recombinant human IFNG, expressed in HEK293 , improves its therapeutic efficacy compared to

5041-445: Was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin , and by others as a product of antigen-stimulated lymphocytes . It was also shown to be produced in human lymphocytes. or tuberculin -sensitized mouse peritoneal lymphocytes challenged with Mantoux test  (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus . Those reports also contained

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