Interferon-stimulated gene

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An interferon-stimulated gene (ISG) is a gene that can be expressed in response to stimulation by interferon.[1][2] Interferons bind to receptors on the surface of a cell, initiating protein signaling pathways within the cell. This interaction leads to the expression of a subset of genes involved in the innate immune system response.[1] ISGs are commonly expressed in response to viral infection, but also during bacterial infection and in the presence of parasites.[2][1]

Expression[]

ISGs are genes whose expression can be stimulated by interferon, but may also be stimulated by other pathways.[1] Interferons are a type of protein called a cytokine, which is produced in response to infection.[3] When released, they signal to infected cells and other nearby cells that a pathogen is present.[3]

This signal is passed from one cell to another by binding of the interferon to a cell surface receptor on a naïve cell.[4] The receptor and interferon are taken inside the cell while bound to initiate expression of ISGs.[4]

Interferon activation of ISGs uses the JAK-STAT signaling pathway to induce transcription of ISGs. ISGs can be divided based on what class of interferon they are activated by: type I, type II, or type III interferon.[1] The protein products of ISGs control pathogen infections.

Specifically, type I and type III interferons are antiviral cytokines, triggering ISGs that combat viral infections.[5] Type I interferons are also involved in bacterial infections; however, they can have both beneficial and harmful effects.[6] The type II interferon class only has one cytokine (IFN-γ), which has some antiviral activity, but is more important in establishing cellular immunity through activating macrophages and promoting major histocompatibility complex (MHC) class II.[7]

All ISG stimulation pathways result in the production of transcription factors.[2][4] Type I and type III interferons produce a protein complex called ISGF3, which acts as a transcription factor, and binds to a promoter sequence called ISRE (interferon stimulated response element).[2][4] Type II interferons produce a transcription factor called GAF, which binds to a promoter sequence called GAS.[2][4] These interactions initiate gene expression.[1] These pathways are also commonly initiated by a Toll-like receptor (TLR) on the cell surface.[2] The number and type of ISGs expressed in response to infection is specific to the infecting pathogen.[2]

Function[]

ISGs have a wide range of functions used to combat infection at all stages of a pathogen’s lifestyle.[1] For a viral infection, examples include: prohibiting entry of the virus into uninfected cells, stopping viral replication, and preventing the virus from leaving an infected cell.[1]

Another ISG function is regulating interferon sensitivity of a cell.[1] The expression of pattern recognition receptors like a TLR or common signaling proteins like those found in the JAK-STAT pathway may be upregulated by interferons, making the cell more sensitive to interferons.[4]

See also[]

References[]

  1. ^ a b c d e f g h i Schneider WM, Chevillotte MD, Rice CM (2014-03-21). "Interferon-stimulated genes: a complex web of host defenses". Annual Review of Immunology. 32 (1): 513–45. doi:10.1146/annurev-immunol-032713-120231. PMC 4313732. PMID 24555472.
  2. ^ a b c d e f g Sen GC, Sarkar SN (2007). "The interferon-stimulated genes: targets of direct signaling by interferons, double-stranded RNA, and viruses". Current Topics in Microbiology and Immunology. 316: 233–50. doi:10.1007/978-3-540-71329-6_12. PMID 17969451.
  3. ^ a b Lazear HM, Schoggins JW, Diamond MS (April 2019). "Shared and Distinct Functions of Type I and Type III Interferons". Immunity. 50 (4): 907–923. doi:10.1016/j.immuni.2019.03.025. PMC 6839410. PMID 30995506.
  4. ^ a b c d e f Hoffmann HH, Schneider WM, Rice CM (March 2015). "Interferons and viruses: an evolutionary arms race of molecular interactions". Trends in Immunology. 36 (3): 124–38. doi:10.1016/j.it.2015.01.004. PMC 4384471. PMID 25704559.
  5. ^ Schoggins JW (2018-03-12). "Recent advances in antiviral interferon-stimulated gene biology". F1000Research. 7: 309. doi:10.12688/f1000research.12450.1. PMC 5850085. PMID 29568506.
  6. ^ Ivashkiv LB, Donlin LT (January 2014). "Regulation of type I interferon responses". Nature Reviews. Immunology. 14 (1): 36–49. doi:10.1038/nri3581. PMC 4084561. PMID 24362405.
  7. ^ Takaoka A, Yanai H (June 2006). "Interferon signalling network in innate defence". Cellular Microbiology. 8 (6): 907–22. doi:10.1111/j.1462-5822.2006.00716.x. PMID 16681834.
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