RIG-I-like receptor

Last updated

RIG-I-like receptors (retinoic acid-inducible gene-I-like receptors, RLRs) are a type of intracellular pattern recognition receptor involved in the recognition of viruses by the innate immune system. [1] [2] RIG-I (retinoic-acid inducible gene or DDX58) is the best characterized receptor within the RIG-I like receptor (RLR) family. Together with MDA5 (melanoma differentiation-associated 5) and LGP2 (laboratory of genetics and physiology 2), this family of cytoplasmic pattern recognition receptors (PRRs) are sentinels for intracellular viral RNA that is a product of viral infection. The RLR receptors provide frontline defence against viral infections in most tissues.

Contents

RLR ligands

The RIG-I receptor prefers to bind short (<2000 bp) single- or double-stranded RNA carrying an uncapped 5’ triphosphate and additional motifs such as poly-uridine rich RNA motifs. [3] [4] RIG-I triggers an immune response to RNA viruses from various families including the paramyxoviruses (e.g. measles), rhabdoviruses (e.g. vesicular stomatitis virus) and orthomyxoviruses (e.g. influenza A). [5] [6] [7] [8] [9] MDA5 ligands are poorly characterized, but the preference is for long double-stranded RNA (>2000 bp), such as the replicative form of picornavirus RNA that is found in picornavirus-infected cells. [10] [11] LGP2 binds to blunt-ended double-stranded RNA of variable length, [12] [13] and also to RNA-bound MDA5 to regulate filament formation. [14] The latter is linked to LGP2's recognition of picornaviruses (e.g. encephalomyocarditis virus), as per MDA5. [15]

Structural features

RIG-I domain architecture. (A) Schematic representation of full-length RIG-I. (B) X-ray crystal structure of RNA-bound RIG-I (PDB: 2YKG ), excluding the CARD domains. RIG-I like receptors Figure 1.jpg
RIG-I domain architecture. (A) Schematic representation of full-length RIG-I. (B) X-ray crystal structure of RNA-bound RIG-I ( PDB: 2YKG ​), excluding the CARD domains.

The RLR receptors are members of the DEAD-box (SF2) helicase family (despite containing a DExD/H motif, rather than the DEAD motif characteristic of the family) and share a common domain architecture. All contain a catalytic helicase core made up of two RecA-like domains. The catalytic helicase core contains at least 9 highly conserved sequence motifs that coordinate ATP and RNA binding and the hydrolysis of ATP to unwind RNA. A C-terminal domain (CTD; InterPro :  IPR021673 ) follows the helicase core and this domain also binds viral RNA. Distinct RNA-binding loops within the CTD of the three RLRs dictate the type of RNA that they can bind. [16] In addition to the helicase core and CTD, RIG-I and MDA5 have two N-terminal CARD (caspase active recruitment domains) that are essential to the initiation of downstream signaling. LGP2 is dissimilar to both RIG-I and MDA5 as it lacks the CARD signaling domains and instead is implicated as a positive and negative regulator of RIG-I and MDA5. [14] [17] [18] [19] [20] [15] [21]

Activation of signaling

In uninfected cells that are absent of viral RNA RIG-I exists in an inactive conformation in which the CARD domains are masked due to their interaction with the CTD. [22] Upon binding RNA, RIG-I changes into a conformation in which the CARD domains are exposed and ‘available’ for signaling. Conversely, the MDA5 CARDs are unhindered in the absence of viral RNA. [23] As a safeguard for RLR activation, the exposed RIG-I and MDA5 CARDs can undergo post-translational modifications (e.g. ubiquitination, phosphorylation) that either positively or negatively regulate downstream signaling.

RIG-I antiviral signaling

Schematic of RLR signaling. Ub denotes ubiquitination, P denotes phosphorylation. RIG-I like receptors Figure 2.jpg
Schematic of RLR signaling. Ub denotes ubiquitination, P denotes phosphorylation.

In the activated state the exposed RIG-I CARD domains interact with the CARD domains of MAVS (mitochondrial antiviral signaling protein, also known as IPS-1, VISA or Cardif) which sits on the outer surface of the mitochondria. This binding event is essential to signaling as it causes MAVS to form large functional aggregates in which TRAF3 (TNF receptor-associated factor 3) and subsequently the IKKε/TBK1 (I-kappa-B kinase-epsilon/TANK-binding kinase 1) complex are recruited. The IKKε/TBK1 complex leads to the activation of the transcription factors interferon regulatory factor 3 (IRF3) and IRF7 which induce type I (including IFNα and IFNβ) and type III interferons (IFN). The type I IFNs bind type I IFN receptors on the surface of the cell that produced them, and also other cell types that express the receptor, to activate JAK-STAT (Janus kinase/signal transducers and activators of transcription) signaling. This leads to the induction of hundreds of interferon stimulated genes (ISGs) that amplify the IFN response. Overall this causes the death of infected cells, the protection of surrounding cells and the activation of the antigen-specific antiviral immune response. Collectively this coordinated antiviral immune response controls the viral infection.

Regulation

As prolonged IFN production is linked to human disease RLR signaling must be tightly regulated. One of various ways that this is achieved is by post-translationally modifying, or tagging, host RLR signaling proteins with phosphate (known as phosphorylation) or ubiquitin (known as ubiquitination). These tags can also be removed, which adds an additional regulatory layer to RLR signaling. These post-translational modifications, and their removal, are prevalent in RLR signaling and even regulate the RIG-I receptor itself. Most famously the RIG-I CARD domain is phosphorylated by protein kinase C-α (PKC-α) and PKC-β in the resting state to negatively regulate signaling. [24] [25] [26] Upon viral infection RIG-I is dephosphorylated by PP1α and PP1γ, [27] permitting the ubiquitination of the RIG-I CARD domain by the E3 ligase TRIM25 to activate the RLR-mediated antiviral immune response. [28] Given post-translational modifications are so pertinent to the activation of RLR signaling, it is not surprising that they are directly, or indirectly, targeted by viruses such as influenza A [29] and measles, [30] respectively, to suppress signaling.

Viral hijacking of RLR signaling

Viruses have evolved ways to subvert RLR signaling to enhance their survival. For example, influenza A virus and West Nile virus (WNV) use their NS1 (nonstructural protein 1) proteins to block RIG-I ubiquitination by TRIM25, or cause RIG-I degradation, respectively, which in turn inhibits IFN production. [29] [31] This outcome is also achieved by the hepatitis C (HCV) NS3/4A protein by cleaving a part of MAVS, [32] and the foot-and-mouth disease virus (FMDV) leader protease (Lpro) which cleaves LGP2. [33] Likewise, dengue virus (DENV) uses its NS2B3, NS2A and NS4B proteins to bind IKKε and prevent IRF3 phosphorylation [34] [35] and its NS4A protein, as per the zika virus, to bind MAVS to block RLR receptor binding. [36] [37] Another prominent example is that of the paramyxovirus V proteins, which directly bind various RLR or downstream signaling proteins including MDA5, LGP2, and STAT, [38] [39] [40] or proteins such as PP1α and PP1γ [30] that negatively regulate RLR signaling.

See also

Related Research Articles

<span class="mw-page-title-main">Interferon</span> Signaling proteins released by host cells in response to the presence of pathogens

Interferons are 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.

Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed mainly by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, as well as by epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.

<span class="mw-page-title-main">Ribonuclease L</span> Enzyme found in humans

Ribonuclease L or RNase L, known sometimes as ribonuclease 4 or 2'-5' oligoadenylate synthetase-dependent ribonuclease, is an interferon (IFN)-induced ribonuclease which, upon activation, destroys all RNA within the cell. RNase L is an enzyme that in humans is encoded by the RNASEL gene.

<span class="mw-page-title-main">Innate immune system</span> Immunity strategy in living beings

The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.

<span class="mw-page-title-main">CARD (domain)</span> Interaction motifs found in a wide array of proteins

Caspase recruitment domains, or caspase activation and recruitment domains (CARDs), are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate the formation of larger protein complexes via direct interactions between individual CARDs. CARDs are found on a strikingly wide range of proteins, including helicases, kinases, mitochondrial proteins, caspases, and other cytoplasmic factors.

<span class="mw-page-title-main">Interferon type I</span> Cytokine

The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cytoband over approximately 400 kb including coding genes for IFNα, IFNω (IFNW1), IFNɛ (IFNE), IFNк (IFNK) and IFNβ (IFNB1), plus 11 IFN pseudogenes.

The type III interferon group is a group of anti-viral cytokines, that consists of four IFN-λ (lambda) molecules called IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4. They were discovered in 2003. Their function is similar to that of type I interferons, but is less intense and serves mostly as a first-line defense against viruses in the epithelium.

<span class="mw-page-title-main">IRF3</span> Protein-coding gene in the species Homo sapiens

Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.

<span class="mw-page-title-main">STAT2</span> Protein-coding gene in Homo sapiens

Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). It functions as a transcription factor downstream of type I interferons. STAT2 sequence identity between mouse and human is only 68%.

<span class="mw-page-title-main">RIG-I</span> Mammalian protein found in humans

RIG-I is a cytosolic pattern recognition receptor (PRR) that can mediate induction of a type-I interferon (IFN1) response. RIG-I is an essential molecule in the innate immune system for recognizing cells that have been infected with a virus. These viruses can include West Nile virus, Japanese Encephalitis virus, influenza A, Sendai virus, flavivirus, and coronaviruses.

<span class="mw-page-title-main">IFNA2</span> Mammalian protein found in Homo sapiens

Interferon alpha-2 is a protein that in humans is encoded by the IFNA2 gene.

<span class="mw-page-title-main">Mitochondrial antiviral-signaling protein</span> Protein-coding gene in the species Homo sapiens

Mitochondrial antiviral-signaling protein (MAVS) is a protein that is essential for antiviral innate immunity. MAVS is located in the outer membrane of the mitochondria, peroxisomes, and mitochondrial-associated endoplasmic reticulum membrane (MAM). Upon viral infection, a group of cytosolic proteins will detect the presence of the virus and bind to MAVS, thereby activating MAVS. The activation of MAVS leads the virally infected cell to secrete cytokines. This induces an immune response which kills the host's virally infected cells, resulting in clearance of the virus.

<span class="mw-page-title-main">TRIM25</span> Protein-coding gene in the species Homo sapiens

Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.

<span class="mw-page-title-main">MDA5</span> Mammalian protein found in Homo sapiens

MDA5 is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses. It is generally believed that MDA5 recognizes double stranded RNA (dsRNA) over 2000nts in length, however it has been shown that whilst MDA5 can detect and bind to cytoplasmic dsRNA, it is also activated by a high molecular weight RNA complex composed of ssRNA and dsRNA. For many viruses, effective MDA5-mediated antiviral responses are dependent on functionally active LGP2. The signaling cascades in MDA5 is initiated via CARD domain. Some observations made in cancer cells show that MDA5 also interacts with cellular RNA is able to induce an autoinflammatory response.

<span class="mw-page-title-main">LGP2</span> Protein-coding gene in the species Homo sapiens

Probable ATP-dependent RNA helicase DHX58 also known as RIG-I-like receptor 3 (RLR-3) or RIG-I-like receptor LGP2 (RLR) is a RIG-I-like receptor dsRNA helicase enzyme that in humans is encoded by the DHX58 gene. The protein encoded by the gene DHX58 is known as LGP2.

Interleukin-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.

<span class="mw-page-title-main">NLRP11</span> Protein-coding gene in the species Homo sapiens

NOD-like receptor family pyrin domain containing 11 is a protein that in humans is encoded by the NLRP11 gene located on the long arm of human chromosome 19q13.42. NLRP11 belongs to the NALP subfamily, part of a large subfamily of CATERPILLER. It is also known as NALP11, PYPAF6, NOD17, PAN10, and CLR19.6

<span class="mw-page-title-main">Stimulator of interferon genes</span> Protein-coding gene in the species Homo sapiens

Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a protein that in humans is encoded by the STING1 gene.

An interferon-stimulated gene (ISG) is a gene that can be expressed in response to stimulation by interferon. 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. ISGs are commonly expressed in response to viral infection, but also during bacterial infection and in the presence of parasites. It's currently estimated that 10% of the human genome is regulated by interferons (IFNs). Interferon stimulated genes can act as an initial response to pathogen invasion, slowing down viral replication and increasing expression of immune signaling complexes. There are three known types of interferon. With approximately 450 genes highly expressed in response to interferon type I. Type I interferon consists of INF-α, INF-β, INF-ω and is expressed in response to viral infection. ISGs induced by type I interferon are associated with viral replication suppression and increase expression of immune signaling proteins. Type II interferon consists only of INF-γ and is associated with controlling intracellular pathogens and tumor suppressor genes. Type III interferon consists of INF-λ and is associated with viral immune response and is key in anti-fungal neutrophil response.

<span class="mw-page-title-main">Viral strategies for immune response evasion</span>

The mammalian immune system has evolved complex methods for addressing and adapting to foreign antigens. At the same time, viruses have co-evolved evasion machinery to address the many ways that host organisms attempt to eradicate them. DNA and RNA viruses use complex methods to evade immune cell detection through disruption of the Interferon Signaling Pathway, remodeling of cellular architecture, targeted gene silencing, and recognition protein cleavage.

References

Open Access logo PLoS transparent.svg This article was adapted from the following source under a CC BY 4.0 license (2019) (reviewer reports): Natalie Borg (2019). "RIG-I like receptors" (PDF). WikiJournal of Science. 2 (1): 1. doi: 10.15347/WJS/2019.001 . ISSN   2470-6345. Wikidata   Q62604415.

  1. ↑ Mahla RS, Reddy MC, Prasad DV, Kumar H (September 2013). "Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology". Frontiers in Immunology. 4: 248. doi: 10.3389/fimmu.2013.00248 . PMC   3759294 . PMID   24032031.
  2. ↑ Offermanns S, Rosenthal W (2008-08-14). Encyclopedia of Molecular Pharmacology, Volume 1. Springer. ISBN   9783540389163 . Retrieved 30 August 2011. The other two families of PRRs, the NOD-like receptors (NLRs) and the RIG-like helicases (RLHs) are soluble receptors present in the cytosol and act as sensors to detect a variety of viral and bacterial products.
  3. ↑ Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, et al. (July 2008). "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5". The Journal of Experimental Medicine. 205 (7): 1601–10. doi:10.1084/jem.20080091. PMC   2442638 . PMID   18591409.
  4. ↑ Saito T, Owen DM, Jiang F, Marcotrigiano J, Gale M (July 2008). "Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA". Nature. 454 (7203): 523–7. Bibcode:2008Natur.454..523S. doi:10.1038/nature07106. PMC   2856441 . PMID   18548002.
  5. ↑ Baum A, Sachidanandam R, García-Sastre A (September 2010). "Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing". Proceedings of the National Academy of Sciences of the United States of America. 107 (37): 16303–8. Bibcode:2010PNAS..10716303B. doi: 10.1073/pnas.1005077107 . PMC   2941304 . PMID   20805493.
  6. ↑ Gitlin L, Barchet W, Gilfillan S, Cella M, Beutler B, Flavell RA, et al. (May 2006). "Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus". Proceedings of the National Academy of Sciences of the United States of America. 103 (22): 8459–64. Bibcode:2006PNAS..103.8459G. doi: 10.1073/pnas.0603082103 . PMC   1464000 . PMID   16714379.
  7. ↑ Hornung V, Ellegast J, Kim S, Brzózka K, Jung A, Kato H, et al. (November 2006). "5'-Triphosphate RNA is the ligand for RIG-I". Science. 314 (5801): 994–7. Bibcode:2006Sci...314..964H. doi: 10.1126/science.1132505 . PMID   17038590. S2CID   22436759.
  8. ↑ Wang H, Ryu WS (July 2010). "Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion". PLOS Pathogens. 6 (7): e1000986. doi: 10.1371/journal.ppat.1000986 . PMC   2904777 . PMID   20657822.
  9. ↑ Schlee M, Roth A, Hornung V, Hagmann CA, Wimmenauer V, Barchet W, et al. (July 2009). "Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus". Immunity. 31 (1): 25–34. doi:10.1016/j.immuni.2009.05.008. PMC   2824854 . PMID   19576794.
  10. ↑ Feng Q, Hato SV, Langereis MA, Zoll J, Virgen-Slane R, Peisley A, et al. (November 2012). "MDA5 detects the double-stranded RNA replicative form in picornavirus-infected cells". Cell Reports. 2 (5): 1187–96. doi:10.1016/j.celrep.2012.10.005. PMC   7103987 . PMID   23142662.
  11. ↑ Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, et al. (May 2006). "Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses". Nature. 441 (7089): 101–5. Bibcode:2006Natur.441..101K. doi:10.1038/nature04734. PMID   16625202. S2CID   2270879.
  12. ↑ Li X, Ranjith-Kumar CT, Brooks MT, Dharmaiah S, Herr AB, Kao C, Li P (May 2009). "The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA". The Journal of Biological Chemistry. 284 (20): 13881–91. doi: 10.1074/jbc.m900818200 . PMC   2679488 . PMID   19278996.
  13. ↑ Murali A, Li X, Ranjith-Kumar CT, Bhardwaj K, Holzenburg A, Li P, Kao CC (June 2008). "Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response". The Journal of Biological Chemistry. 283 (23): 15825–33. doi: 10.1074/jbc.m800542200 . PMC   2414291 . PMID   18411269.
  14. 1 2 Bruns AM, Leser GP, Lamb RA, Horvath CM (September 2014). "The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly". Molecular Cell. 55 (5): 771–81. doi:10.1016/j.molcel.2014.07.003. PMC   4156907 . PMID   25127512.
  15. 1 2 Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, et al. (January 2010). "LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses". Proceedings of the National Academy of Sciences of the United States of America. 107 (4): 1512–7. Bibcode:2010PNAS..107.1512S. doi: 10.1073/pnas.0912986107 . PMC   2824407 . PMID   20080593.
  16. ↑ Takahasi K, Kumeta H, Tsuduki N, Narita R, Shigemoto T, Hirai R, et al. (June 2009). "Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors". The Journal of Biological Chemistry. 284 (26): 17465–74. doi: 10.1074/jbc.m109.007179 . PMC   2719387 . PMID   19380577.
  17. ↑ Childs KS, Randall RE, Goodbourn S (2013-05-09). "LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA". PLOS ONE. 8 (5): e64202. Bibcode:2013PLoSO...864202C. doi: 10.1371/journal.pone.0064202 . PMC   3650065 . PMID   23671710.
  18. ↑ Komuro A, Horvath CM (December 2006). "RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2". Journal of Virology. 80 (24): 12332–42. doi:10.1128/jvi.01325-06. PMC   1676302 . PMID   17020950.
  19. ↑ Parisien JP, Lenoir JJ, Mandhana R, Rodriguez KR, Qian K, Bruns AM, Horvath CM (June 2018). "RNA sensor LGP2 inhibits TRAF ubiquitin ligase to negatively regulate innate immune signaling". EMBO Reports. 19 (6): e45176. doi:10.15252/embr.201745176. PMC   5989757 . PMID   29661858.
  20. ↑ Saito T, Hirai R, Loo YM, Owen D, Johnson CL, Sinha SC, et al. (January 2007). "Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2". Proceedings of the National Academy of Sciences of the United States of America. 104 (2): 582–7. Bibcode:2007PNAS..104..582S. doi: 10.1073/pnas.0606699104 . PMC   1766428 . PMID   17190814.
  21. ↑ Uchikawa E, Lethier M, Malet H, Brunel J, Gerlier D, Cusack S (May 2016). "Structural Analysis of dsRNA Binding to Anti-viral Pattern Recognition Receptors LGP2 and MDA5". Molecular Cell. 62 (4): 586–602. doi:10.1016/j.molcel.2016.04.021. PMC   4885022 . PMID   27203181.
  22. ↑ Luo D, Ding SC, Vela A, Kohlway A, Lindenbach BD, Pyle AM (October 2011). "Structural insights into RNA recognition by RIG-I". Cell. 147 (2): 409–22. doi:10.1016/j.cell.2011.09.023. PMC   3222294 . PMID   22000018.
  23. ↑ Berke IC, Modis Y (April 2012). "MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA". The EMBO Journal. 31 (7): 1714–26. doi:10.1038/emboj.2012.19. PMC   3321199 . PMID   22314235.
  24. ↑ Gack MU, Nistal-Villán E, Inn KS, García-Sastre A, Jung JU (April 2010). "Phosphorylation-mediated negative regulation of RIG-I antiviral activity". Journal of Virology. 84 (7): 3220–9. doi:10.1128/jvi.02241-09. PMC   2838087 . PMID   20071582.
  25. ↑ Maharaj NP, Wies E, Stoll A, Gack MU (February 2012). "Conventional protein kinase C-α (PKC-α) and PKC-β negatively regulate RIG-I antiviral signal transduction". Journal of Virology. 86 (3): 1358–71. doi:10.1128/jvi.06543-11. PMC   3264329 . PMID   22114345.
  26. ↑ Nistal-Villán E, Gack MU, Martínez-Delgado G, Maharaj NP, Inn KS, Yang H, et al. (June 2010). "Negative role of RIG-I serine 8 phosphorylation in the regulation of interferon-beta production". The Journal of Biological Chemistry. 285 (26): 20252–61. doi: 10.1074/jbc.m109.089912 . PMC   2888438 . PMID   20406818.
  27. ↑ Wies E, Wang MK, Maharaj NP, Chen K, Zhou S, Finberg RW, Gack MU (March 2013). "Dephosphorylation of the RNA sensors RIG-I and MDA5 by the phosphatase PP1 is essential for innate immune signaling". Immunity. 38 (3): 437–49. doi:10.1016/j.immuni.2012.11.018. PMC   3616631 . PMID   23499489.
  28. ↑ Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, et al. (April 2007). "TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity". Nature. 446 (7138): 916–920. Bibcode:2007Natur.446..916G. doi:10.1038/nature05732. PMID   17392790. S2CID   4404114.
  29. 1 2 Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, et al. (May 2009). "Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I". Cell Host & Microbe. 5 (5): 439–49. doi:10.1016/j.chom.2009.04.006. PMC   2737813 . PMID   19454348.
  30. 1 2 Davis ME, Wang MK, Rennick LJ, Full F, Gableske S, Mesman AW, et al. (July 2014). "Antagonism of the phosphatase PP1 by the measles virus V protein is required for innate immune escape of MDA5". Cell Host & Microbe. 16 (1): 19–30. doi:10.1016/j.chom.2014.06.007. PMC   4120867 . PMID   25011105.
  31. ↑ Zhang HL, Ye HQ, Liu SQ, Deng CL, Li XD, Shi PY, Zhang B (September 2017). "West Nile Virus NS1 Antagonizes Interferon Beta Production by Targeting RIG-I and MDA5". Journal of Virology. 91 (18). doi:10.1128/jvi.02396-16. PMC   5571242 . PMID   28659477.
  32. ↑ Li XD, Sun L, Seth RB, Pineda G, Chen ZJ (December 2005). "Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity". Proceedings of the National Academy of Sciences of the United States of America. 102 (49): 17717–22. doi: 10.1073/pnas.0508531102 . PMC   1308909 . PMID   16301520.
  33. ↑ Rodríguez Pulido M, Sánchez-Aparicio MT, Martínez-Salas E, García-Sastre A, Sobrino F, Sáiz M (June 2018). "Innate immune sensor LGP2 is cleaved by the Leader protease of foot-and-mouth disease virus". PLOS Pathogens. 14 (6): e1007135. doi: 10.1371/journal.ppat.1007135 . PMC   6042790 . PMID   29958302.
  34. ↑ Angleró-Rodríguez YI, Pantoja P, Sariol CA (January 2014). "Dengue virus subverts the interferon induction pathway via NS2B/3 protease-IκB kinase epsilon interaction". Clinical and Vaccine Immunology. 21 (1): 29–38. doi:10.1128/cvi.00500-13. PMC   3910921 . PMID   24173023.
  35. ↑ Dalrymple NA, Cimica V, Mackow ER (May 2015). "Dengue Virus NS Proteins Inhibit RIG-I/MAVS Signaling by Blocking TBK1/IRF3 Phosphorylation: Dengue Virus Serotype 1 NS4A Is a Unique Interferon-Regulating Virulence Determinant". mBio. 6 (3): e00553-15. doi:10.1128/mbio.00553-15. PMC   4436066 . PMID   25968648.
  36. ↑ He Z, Zhu X, Wen W, Yuan J, Hu Y, Chen J, et al. (August 2016). "Dengue Virus Subverts Host Innate Immunity by Targeting Adaptor Protein MAVS". Journal of Virology. 90 (16): 7219–7230. doi:10.1128/jvi.00221-16. PMC   4984625 . PMID   27252539.
  37. ↑ Ma J, Ketkar H, Geng T, Lo E, Wang L, Xi J, et al. (2018-06-25). "Zika Virus Non-structural Protein 4A Blocks the RLR-MAVS Signaling". Frontiers in Microbiology. 9: 1350. doi: 10.3389/fmicb.2018.01350 . PMC   6026624 . PMID   29988497.
  38. ↑ Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE (December 2004). "The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter". Proceedings of the National Academy of Sciences of the United States of America. 101 (49): 17264–9. Bibcode:2004PNAS..10117264A. doi: 10.1073/pnas.0407639101 . PMC   535396 . PMID   15563593.
  39. ↑ Childs K, Stock N, Ross C, Andrejeva J, Hilton L, Skinner M, et al. (March 2007). "mda-5, but not RIG-I, is a common target for paramyxovirus V proteins". Virology. 359 (1): 190–200. doi: 10.1016/j.virol.2006.09.023 . PMID   17049367.
  40. ↑ Rodriguez KR, Horvath CM (July 2014). "Paramyxovirus V protein interaction with the antiviral sensor LGP2 disrupts MDA5 signaling enhancement but is not relevant to LGP2-mediated RLR signaling inhibition". Journal of Virology. 88 (14): 8180–8. doi:10.1128/jvi.00737-14. PMC   4097766 . PMID   24829334.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.