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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages

  • Lee, Wook-Bin (Korean Institute of Science and Technology (KIST), Gangneung Institute of Natural Products) ;
  • Choi, Won Young (Department of Integrated Omics for Biomedical Science, Graduate School, Yonsei University) ;
  • Lee, Dong-Hyun (Department of Integrated Omics for Biomedical Science, Graduate School, Yonsei University) ;
  • Shim, Hyeran (Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University) ;
  • KimHa, Jeongsil (Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University) ;
  • Kim, Young-Joon (Department of Integrated Omics for Biomedical Science, Graduate School, Yonsei University)
  • Received : 2018.06.15
  • Accepted : 2018.07.09
  • Published : 2019.02.28
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Abstract

Upon viral infection, the 2', 5'-oligoadenylate synthetase (OAS)-ribonuclease L (RNaseL) system works to cleave viral RNA, thereby blocking viral replication. However, it is unclear whether OAS proteins have a role in regulating gene expression. Here, we show that OAS1 and OAS3 act as negative regulators of the expression of chemokines and interferon-responsive genes in human macrophages. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) technology was used to engineer human myeloid cell lines in which the OAS1 or OAS3 gene was deleted. Neither OAS1 nor OAS3 was exclusively responsible for the degradation of rRNA in macrophages stimulated with poly(I:C), a synthetic surrogate for viral double-stranded (ds)RNA. An mRNA sequencing analysis revealed that genes related to type I interferon signaling and chemokine activity were increased in $OAS1^{-/-}$ and $OAS3^{-/-}$ macrophages treated with intracellular poly(I:C). Indeed, retinoic-acid-inducible gene (RIG)-I- and interferon-induced helicase C domain-containing protein (IFIH1 or MDA5)-mediated induction of chemokines and interferon-stimulated genes was regulated by OAS3, but Toll-like receptor 3 (TLR3)- and TLR4-mediated induction of those genes was modulated by OAS1 in macrophages. However, stimulation of these cells with type I interferons had no effect on OAS1- or OAS3-mediated chemokine secretion. These data suggest that OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages.

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References

  1. Kawai T and Akira S (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34, 637-650 https://doi.org/10.1016/j.immuni.2011.05.006
  2. Justesen J, Hartmann R and Kjeldgaard NO (2000) Gene structure and function of the 2'-5'-oligoadenylate synthetase family. Cell Mol Life Sci 57, 1593-1612 https://doi.org/10.1007/PL00000644
  3. Kristiansen H, Gad HH, Eskildsen-Larsen S, Despres P and Hartmann R (2011) The oligoadenylate synthetase family: an ancient protein family with multiple antiviral activities. J Interferon Cytokine Res 31, 41-47 https://doi.org/10.1089/jir.2010.0107
  4. Dong B and Silverman RH (1995) 2-5A-dependent RNase molecules dimerize during activation by 2-5A. J Biol Chem 270, 4133-4137 https://doi.org/10.1074/jbc.270.8.4133
  5. Hovanessian AG and Justesen J (2007) The human 2'-5'oligoadenylate synthetase family: unique interferoninducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation. Biochimie 89, 779-788 https://doi.org/10.1016/j.biochi.2007.02.003
  6. Alagarasu K, Honap T, Damle IM, Mulay AP, Shah PS and Cecilia D (2013) Polymorphisms in the oligoadenylate synthetase gene cluster and its association with clinical outcomes of dengue virus infection. Infect Genet Evol 14, 390-395 https://doi.org/10.1016/j.meegid.2012.12.021
  7. Lim JK, Lisco A, McDermott DH et al (2009) Genetic variation in OAS1 is a risk factor for initial infection with West Nile virus in man. PLoS Pathog 5, e1000321 https://doi.org/10.1371/journal.ppat.1000321
  8. Behera AK, Kumar M, Lockey RF and Mohapatra SS (2002) 2'-5' Oligoadenylate synthetase plays a critical role in interferon-gamma inhibition of respiratory syncytial virus infection of human epithelial cells. J Biol Chem 277, 25601-25608 https://doi.org/10.1074/jbc.M200211200
  9. Cai Y, Chen Q, Zhou W et al (2014) Association analysis of polymorphisms in OAS1 with susceptibility and severity of hand, foot and mouth disease. Int J Immunogenet 41, 384-392 https://doi.org/10.1111/iji.12134
  10. Donovan J, Dufner M and Korennykh A (2013) Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1. Proc Natl Acad Sci U S A 110, 1652-1657 https://doi.org/10.1073/pnas.1218528110
  11. Ibsen MS, Gad HH, Thavachelvam K, Boesen T, Despres P and Hartmann R (2014) The 2'-5'-oligoadenylate synthetase 3 enzyme potently synthesizes the 2'-5'-oligoadenylates required for RNase L activation. J Virol 88, 14222-14231 https://doi.org/10.1128/JVI.01763-14
  12. Donovan J, Whitney G, Rath S and Korennykh A (2015) Structural mechanism of sensing long dsRNA via a noncatalytic domain in human oligoadenylate synthetase 3. Proc Natl Acad Sci U S A 112, 3949-3954 https://doi.org/10.1073/pnas.1419409112
  13. Li Y, Banerjee S, Wang Y et al (2016) Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses. Proc Natl Acad Sci U S A 113, 2241-2246 https://doi.org/10.1073/pnas.1519657113
  14. Zhao L, Birdwell LD, Wu A et al (2013) Cell-type-specific activation of the oligoadenylate synthetase-RNase L pathway by a murine coronavirus. J Virol 87, 8408-8418 https://doi.org/10.1128/JVI.00769-13
  15. Banerjee S, Chakrabarti A, Jha BK, Weiss SR and Silverman RH (2014) Cell-type-specific effects of RNase L on viral induction of beta interferon. MBio 5, e00856-00814
  16. Malaguarnera L, Nunnari G and Di Rosa M (2016) Nuclear import sequence identification in hOAS3 protein. Inflamm Res 65, 895-904 https://doi.org/10.1007/s00011-016-0972-8
  17. Shen S, Loh TJ, Shen H, Zheng X and Shen H (2017) CRISPR as a strong gene editing tool. BMB Rep 50, 20-24 https://doi.org/10.5483/BMBRep.2017.50.1.128
  18. Takeuchi O and Akira S (2008) MDA5/RIG-I and virus recognition. Curr Opin Immunol 20, 17-22 https://doi.org/10.1016/j.coi.2008.01.002
  19. Takeuchi O and Akira S (2010) Pattern recognition receptors and inflammation. Cell 140, 805-820 https://doi.org/10.1016/j.cell.2010.01.022
  20. Yoneyama M and Fujita T (2009) RNA recognition and signal transduction by RIG-I-like receptors. Immunol Rev 227, 54-65 https://doi.org/10.1111/j.1600-065X.2008.00727.x
  21. Das A, Chai JC, Kim SH et al (2015) Transcriptome sequencing of microglial cells stimulated with TLR3 and TLR4 ligands. BMC Genomics 16, 517 https://doi.org/10.1186/s12864-015-1728-5
  22. Takeshita F, Suzuki K, Sasaki S, Ishii N, Klinman DM and Ishii KJ (2004) Transcriptional regulation of the human TLR9 gene. J Immunol 173, 2552-2561 https://doi.org/10.4049/jimmunol.173.4.2552
  23. Mantovani A, Bonecchi R and Locati M (2006) Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol 6, 907-918 https://doi.org/10.1038/nri1964
  24. Samuel MA, Whitby K, Keller BC et al (2006) PKR and RNase L contribute to protection against lethal West Nile Virus infection by controlling early viral spread in the periphery and replication in neurons. J Virol 80, 7009-7019 https://doi.org/10.1128/JVI.00489-06
  25. Kristiansen H, Scherer CA, McVean M et al (2010) Extracellular 2'-5' oligoadenylate synthetase stimulates RNase L-independent antiviral activity: a novel mechanism of virus-induced innate immunity. J Virol 84, 11898- 11904 https://doi.org/10.1128/JVI.01003-10
  26. Kim TH and Lee HK (2014) Innate immune recognition of respiratory syncytial virus infection. BMB Rep 47, 184-191 https://doi.org/10.5483/BMBRep.2014.47.4.050
  27. Li S, Wang L, Berman M, Kong YY and Dorf ME (2011) Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity 35, 426-440 https://doi.org/10.1016/j.immuni.2011.06.014