Identification of new type I interferonstimulated genes and investigation of their involvement in IFN-β activation

doi:10.1007/s13238-018-0511-1

Protein Cell

2018, Vol. 9

Issue (9) : 799-807 https://doi.org/10.1007/s13238-018-0511-1

RESEARCH ARTICLE

Identification of new type I interferonstimulated genes and investigation of their involvement in IFN-β activation

Xiaolin Zhang^1,², Wei Yang¹, Xinlu Wang¹, Xuyuan Zhang¹, Huabin Tian¹, Hongyu Deng¹, Liguo Zhang¹, Guangxia Gao^1,²(

)

¹. CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
². University of Chinese Academy of Sciences, Beijing 100049, China

Download: PDF(741 KB)
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

Virus infection induces the production of type I interferons (IFNs). IFNs bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the up-regulation of interferon-stimulated genes (ISGs). ISGs play very important roles in innate immunity through a variety of mechanisms. Although hundreds of ISGs have been identified, it is commonly recognized that more ISGs await to be discovered. The aim of this study was to identify new ISGs and to probe their roles in regulating virus-induced type I IFN production. We used consensus interferon (Con-IFN), an artificial alpha IFN that was shown to be more potent than naturally existing type I IFN, to treat three human immune cell lines, CEM, U937 and Daudi cells. Microarray analysis was employed to identify those genes whose expressions were up-regulated. Six hundred and seventeen genes were up-regulated more than 3-fold. Out of these 617 genes, 138 were not previously reported as ISGs and thus were further pursued. Validation of these 138 genes using quantitative reverse transcription PCR (qRT-PCR) confirmed 91 genes. We screened 89 genes for those involved in Sendai virus (SeV)-induced IFN-β promoter activation, and PIM1 was identified as one whose expression inhibited SeV-mediated IFN-β activation. We provide evidence indicating that PIM1 specifically inhibits RIG-I- and MDA5-mediated IFN-β signaling. Our results expand the ISG library and identify PIM1 as an ISG that participates in the regulation of virus-induced type I interferon production.

Keywords interferon-stimulated genes IFN-β signaling PIM1 RIG-I MDA5

Corresponding Author(s): Guangxia Gao

Issue Date: 21 September 2018

Cite this article:

Xiaolin Zhang,Wei Yang,Xinlu Wang, et al. Identification of new type I interferonstimulated genes and investigation of their involvement in IFN-β activation[J]. Protein Cell, 2018, 9(9): 799-807.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-018-0511-1
https://academic.hep.com.cn/pac/EN/Y2018/V9/I9/799

1	Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296:1653–1655 https://doi.org/10.1126/science.1071545
2	Alton K (1983) Production, characterization and biological effects of recombinant DNA derived human interferon and interferon analogs. Biol Interferon Syst119–128.
3	Bachmann M, Moroy T (2005) The serine/threonine kinase Pim-1. Int J Biochem Cell Biol 37:726–730 https://doi.org/10.1016/j.biocel.2004.11.005
4	Blatt LM, Davis JM, Klein SB, Taylor MW (1996) The biologic activity and molecular characterization of a novel synthetic interferonalpha species, consensus interferon. J Interferon Cytokine Res 16:489–499 https://doi.org/10.1089/jir.1996.16.489
5	Calcaterra S, Horejsh D, Abbate I, Lalle E, Antonucci Get al. (2006) Interferon related gene expression in PBMC in vitro exposed to IFN-alpha as a predictor of response to therapy for HCV-infected patients. Hepatology 44:304a–304a
6	Chen JB, Baig E, Fish EN (2004) Diversity and relatedness among the type I interferons. J Interferon Cytokine Res 24:687–698 https://doi.org/10.1089/jir.2004.24.687
7	de Veer MJ, Holko M, Frevel M,Walker E, Der Set al. (2001) Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol 69:912–920
8	de Vries M, Smithers NP, Howarth PH, Nawijn MC, Davies DE (2015) Inhibition of Pim1 kinase reduces viral replication in primary bronchial epithelial cells. Eur Respir J 45:1745–1748 https://doi.org/10.1183/09031936.00206514
9	de Weerd NA, Samarajiwa SA, Hertzog PJ (2007) Type I interferon receptors: biochemistry and biological functions. J Biol Chem 282:20053–20057 https://doi.org/10.1074/jbc.R700006200
10	Der SD, Zhou A, Williams BR, Silverman RH (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci U S A 95:15623–15628 https://doi.org/10.1073/pnas.95.26.15623
11	Diao F, Li S, Tian Y, Zhang M, Xu LGet al. (2007) Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase. Proc Natl Acad Sci U S A 104:11706–11711 https://doi.org/10.1073/pnas.0700544104
12	Fu XY, Schindler C, Improta T, Aebersold R, Darnell JE Jr (1992) The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc Natl Acad Sci U S A 89:7840–7843 https://doi.org/10.1073/pnas.89.16.7840
13	Gack MU, Shin YC, Joo CH, Urano T, Liang Cet al. (2007) TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446:916–920 https://doi.org/10.1038/nature05732
14	Hilkens CMU, Schlaak JF, Kerr IM (2003) Differential responses to IFN-alpha subtypes in human T cells and dendritic cells. J Immunol 171:5255–5263 https://doi.org/10.4049/jimmunol.171.10.5255
15	Indraccolo S, Pfeffer U, Minuzzo S, Esposito G, Roni Vet al. (2007) Identification of genes selectively regulated by IFNs in endothelial cells. J Immunol 178:1122–1135 https://doi.org/10.4049/jimmunol.178.2.1122
16	Ivashkiv LB, Donlin LT (2014) Regulation of type I interferon responses. Nat Rev Immunol 14:36–49 https://doi.org/10.1038/nri3581
17	Kawai T, Takahashi K, Sato S, Coban C, Kumar Het al. (2005) IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6:981–988 https://doi.org/10.1038/ni1243
18	Klein ML, Bartley TD, Lai P, Lu HS (1988) Structural characterization of recombinant consensus interferon-α. J Chromatogr A 454:205–215 https://doi.org/10.1016/S0021-9673(00)88614-8
19	Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen Met al. (2003) IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4:69–77 https://doi.org/10.1038/ni875
20	Liu SY, Sanchez DJ, Aliyari R, Lu S, Cheng G (2012) Systematic identification of type I and type II interferon-induced antiviral factors. Proc Natl Acad Sci U S A 109:4239–4244 https://doi.org/10.1073/pnas.1114981109
21	Maharaj NP, Wies E, Stoll A, Gack MU (2012) Conventional protein kinase C-alpha (PKC-alpha) and PKC-beta negatively regulate RIG-I antiviral signal transduction. J Virol 86:1358–1371 https://doi.org/10.1128/JVI.06543-11
22	Martensen PM, Justesen J (2004) Small ISGs coming forward. J Interferon Cytokine Res 24:1–19 https://doi.org/10.1089/107999004772719864
23	Meylan E,Curran J, Hofmann K, Moradpour D, Binder Met al. (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437:1167–1172 https://doi.org/10.1038/nature04193
24	Narayan K, Waggoner L, Pham ST, Hendricks GL, Waggoner SNet al. (2014) TRIM13 is a negative regulator of MDA5-mediated type I interferon production. J Virol 88:10748–10757 https://doi.org/10.1128/JVI.02593-13
25	Pestka S (2007) The interferons: 50 years after their discovery, there is much more to learn. J Biol Chem 282:20047–20051 https://doi.org/10.1074/jbc.R700004200
26	Pestka S, Kotenko SV, Muthukumaran G, Izotova LS, Cook JRet al. (1997) The interferon gamma (IFN-gamma) receptor: a paradigm for the multichain cytokine receptor. Cytokine Growth Factor Rev 8:189–206 https://doi.org/10.1016/S1359-6101(97)00009-9
27	Pfeffer LM, Eisenkraft BL, Reich NC, Improta T, Baxter Get al. (1991) Transmembrane signaling by interferon alpha involves diacylglycerol production and activation of the epsilon isoform of protein kinase C in Daudi cells. Proc Natl Acad Sci U S A 88:7988–7992 https://doi.org/10.1073/pnas.88.18.7988
28	Quicke KM, Diamond MS, Suthar MS (2017) Negative regulators of the RIG-I-like receptor signaling pathway. Eur J Immunol 47:615–628 https://doi.org/10.1002/eji.201646484
29	Rajsbaum R, Stoye JP, O’Garra A (2008) Type I interferondependent and-independent expression of tripartite motif proteins in immune cells. Eur J Immunol 38:619–630 https://doi.org/10.1002/eji.200737916
30	Salamon D, Adori M, He M, Bonelt P, Severinson Eet al. (2012) Type I interferons directly down-regulate BCL-6 in primary and transformed germinal center B cells: differential regulation in B cell lines derived from endemic or sporadic Burkitt’s lymphoma. Cytokine 57:360–371 https://doi.org/10.1016/j.cyto.2011.12.001
31	Schneider WM, Chevillotte MD, Rice CM (2014) Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol 32:513–545 https://doi.org/10.1146/annurev-immunol-032713-120231
32	Schoggins JW, Rice CM (2011) Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol 1:519–525 https://doi.org/10.1016/j.coviro.2011.10.008
33	Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CTet al. (2011) A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472:481–485 https://doi.org/10.1038/nature09907
34	Seth RB, Sun L, Ea CK, Chen ZJ (2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122:669–682 https://doi.org/10.1016/j.cell.2005.08.012
35	Sun Z, Ren H, Liu Y, Teeling JL, Gu J (2011) Phosphorylation of RIGI by casein kinase II inhibits its antiviral response. J Virol 85:1036–1047 https://doi.org/10.1128/JVI.01734-10
36	Uze G, Schreiber G, Piehler J, Pellegrini S (2007) The receptor of the type I interferon family. Curr Top Microbiol Immunol 316:71–95 https://doi.org/10.1007/978-3-540-71329-6_5
37	Versteeg GA, Rajsbaum R, Sanchez-Aparicio MT, Maestre AM, Valdiviezo Jet al. (2013) The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune patternrecognition receptors. Immunity 38:384–398 https://doi.org/10.1016/j.immuni.2012.11.013
38	Wies E, Wang MK, Maharaj NP, Chen K, Zhou Set al. (2013) Dephosphorylation of the RNA sensors RIG-I and MDA5 by the phosphatase PP1 is essential for innate immune signaling. Immunity 38:437–449 https://doi.org/10.1016/j.immuni.2012.11.018
39	Wilkins C, Gale M Jr (2010) Recognition of viruses by cytoplasmic sensors. Curr Opin Immunol 22:41–47 https://doi.org/10.1016/j.coi.2009.12.003
40	Xu LG, Wang YY, Han KJ, Li LY, Zhai Zet al. (2005) VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 19:727–740 https://doi.org/10.1016/j.molcel.2005.08.014
41	Yap DY, Lai KN (2010) Cytokines and their roles in the pathogenesis of systemic lupus erythematosus: from basics to recent advances. J Biomed Biotechnol 2010:365083 https://doi.org/10.1155/2010/365083

[1]

PAC-0799-17478-GGX_suppl_1

Download

[1]	Xiao-xiao Xu, Han Wan, Li Nie, Tong Shao, Li-xin Xiang, Jian-zhong Shao. RIG-I: a multifunctional protein beyond a pattern recognition receptor[J]. Protein Cell, 2018, 9(3): 246-253.
[2]	Miao Feng, Zhanyu Ding, Liang Xu, Liangliang Kong, Wenjia Wang, Shi Jiao, Zhubing Shi, Mark I. Greene, Yao Cong, Zhaocai Zhou. Structural and biochemical studies of RIG-I antiviral signaling[J]. Prot Cell, 2013, 4(2): 142-154.
[3]	Feng Liu, Jun Gu. Retinoic acid inducible gene-I, more than a virus sensor[J]. Prot Cell, 2011, 2(5): 351-357.
[4]	Zhiqiang Mi, Jihuan Fu, Yanbao Xiong, Hong Tang, . SUMOylation of RIG-I positively regulates the type I interferon signaling[J]. Protein Cell, 2010, 1(3): 275-283.

Viewed

Full text

Abstract

Cited

Shared

Discussed