泛素样蛋白ISG15抗病毒机制研究进展Advances in Ubiquitin-like Protein ISG15-mediated Anti-viral Response
朱紫祥,魏建超,史子学,吴开宝,马志永
摘要(Abstract):
ISG15(Interferon stimulated gene 15,ISG15)蛋白是由干扰素诱导产生的一种泛素样蛋白分子,分子量大小约为15kD。ISG15同泛素分子相类似可以被共价结合于其他蛋白分子上,这种现象称为ISG化(ISGylation)现象。ISG化系统包括ISG15、UBE1L、UBCH8和HERC5四类蛋白分子,协同完成ISG化过程。ISG15及ISG化系统在抗病毒反应中具有重要作用。近几年对于ISG15的抗病毒作用和机制的研究已经有了很大的突破,ISG15的抗病毒作用也越来越受到人们重视,了解清楚ISG15抗病毒机制对于研制新的抗病毒药物及提出新的抗病毒策略具有重要意义。本文对ISG15在不同种病毒中的抗病毒机制研究进展进行了简要综述。
关键词(KeyWords): ISG15;ISG化;抗病毒作用
基金项目(Foundation): 转基因生物新品种培育科技重大专项(2009ZX08010-022B);; 上海市基础研究重点项目(10JC1417300)
作者(Author): 朱紫祥,魏建超,史子学,吴开宝,马志永
DOI: 10.13242/j.cnki.bingduxuebao.002246
参考文献(References):
- [1]de Veer M J,Holko M,Frevel M,et al.Functional classification of interferon-stimulated genes identified u-sing microarrays[J].J Leukocyte Biol,2001,69(6):912-920.
- [2]Zhang D,Zhang D E.Interferon-stimulated gene15and the protein ISGylation system[J].J Interferon Cytokine Res,2011,31(1):119-130.
- [3]Skaug B,Chen Z J.Emerging role of ISG15in antiviral immunity[J].Cell,2010,143(2):187-190.
- [4]Hsiang T Y,Zhao C,Krug R M.Interferon-induced ISG15conjugation inhibits influenza A virus gene ex-pression and replication in human cells[J].J Virol,2009,83(12):5971-5977.
- [5]Jeon Y J,Yoo H M,Chung C H.ISG15and immune diseases[J].Biochim Biophys Acta,2010,1802(5):485-496.
- [6]Zhao C,Denison C,Huibregtse J M,et al.Human ISG15conjugation targets both IFN-induced and consti-tutively expressed proteins functioning in diverse cellu-lar pathways[J].Proc Natl Acad Sci U S A,2005,102(29):10200-10205.
- [7]Sadler A J,Williams B R.Interferon-inducible antiviral effectors[J].Nat Rev Immunol,2008,8(7):559-568.
- [8]Pitha-Rowe I F,Pitha P M.Viral defense,carcinogene-sis and ISG15:novel roles for an old ISG[J].Cytokine Growth F R,2007,18(5-6):409-417.
- [9]Sen G C,Sarkar S N.The interferon-stimulated genes:targets of direct signaling by interferons,double-stran-ded RNA,and viruses[J].Curr Top Microbiology,2007,316:233-250.
- [10]Kim J H,Luo J K,Zhang D E.The level of hepatitis B virus replication is not affected by protein ISG15 modification but is reduced by inhibition of UBP43(USP18)expression[J].J Immunol,2008,181(9):6467-6472.
- [11]Hsiao N W,Chen J W,Yang T C,et al.ISG15over-expression inhibits replication of the Japanese encepha-litis virus in human medulloblastoma cells[J].Antiviral Res,2010,85(3):504-511.
- [12]Osiak A,Utermohlen O,Niendorf S,et al.ISG15,an interferon-stimulated ubiquitin-like protein,is not es-sential for STAT1signaling and responses against ve-sicular stomatitis and lymphocytic choriomeningitis vi-rus[J].Mol Cell Biol,2005,25(15):6338-6345.
- [13]Moore E C,Barber J,Tripp R A.Respiratory syncyti-al virus(RSV)attachment and nonstructural proteins modify the type I interferon response associated with suppressor of cytokine signaling(SOCS)proteins and IFN-stimulated gene-15(ISG15)[J].J Virol,2008,5:116.
- [14]Lenschow D J,Lai C,Frias-Staheli N,et al.IFN-stimulated gene15functions as a critical antiviral mole-cule against influenza,herpes,and Sindbis viruses[J].Proc Natl Acad Sci U S A,2007,104(4):1371-1376.
- [15]Giannakopoulos N V,Arutyunova E,Lai C,et al.ISG15Arg151and the ISG15-conjugating enzyme UbE1L are important for innate immune control of Sindbis virus[J].J Virol,2009,83(4):1602-1610.
- [16]Shi H X,Yang K,Liu X,et al.Positive regulation of interferon regulatory factor3activation by Herc5via ISG15modification[J].Mol Cell Biol,2010,30(10):2424-2436.
- [17]Pitha P M,Rowe W P,Oxman M N.Effect of inter-feron on exogenous,endogenous,and chroniv murine leukemia virus infection[J].Virology,1976,70(2):324-338.
- [18]Pitha P M,Staal S P,Bolognesi D P,et al.Effect of interferon on murine leukemia virus infection.II.Syn-thesis of viral components in exogenous infection[J].Virology,1977,79(1):1-13.
- [19]Kunzi M S,Pitha P M.Interferon targeted genes in host defense[J].Autoimmunity,2003,36(8):457-461.
- [20]Kunzi M S,Pitha P M.Role of interferon-stimulated gene ISG-15in the interferon-omega-mediated inhibi-tion of human immunodeficiency virus replication[J].J Leukocyte Biol,1996,16(11):919-927.
- [21]Okumura A,Lu G,Pitha-Rowe I,et al.Innate antivi-ral response targets HIV-1release by the induction of ubiquitin-like protein ISG15[J].Proc Natl Acad Sci U S A,2006,103(5):1440-1445.
- [22]Kuang Z,Seo E J,Leis J.Mechanism of Inhibition of retrovirus release from cells by interferon-induced Gene ISG15[J].J Virol,2011,85(14):7153-7161.
- [23]Malakhova O A,Zhang D E.ISG15inhibits Nedd4 ubiquitin E3activity and enhances the innate antiviral response[J].J Biol Chem,2008,283(14):8783-8787.
- [24]Okumura A,Pitha P M,Harty R N.ISG15inhibits Ebola VP40VLP budding in an L-domain-dependent manner by blocking Nedd4ligase activity[J].Proc Natl Acad Sci U S A,2008,105(10):3974-3979.
- [25]Timmins J,Schoehn G,Ricard-Blum S,et al.Ebola virus matrix protein VP40interaction with human cel-lular factors Tsg101and Nedd4[J].J Mol Biol,2003,326(2):493-502.
- [26]Taylor G M,Hanson P I,Kielian M.Ubiquitin deple-tion and dominant-negative VPS4inhibit rhabdovirus budding without affecting alphavirus budding[J].J Virol,2007,81(24):13631-13639.
- [27]Yasuda J,Hunter E,Nakao M,et al.Functional in-volvement of a novel Nedd4-like ubiquitin ligase on ret-rovirus budding[J].EMBO Rep,2002,3(7):636-640.
- [28]Yuan W,Krug R M.Influenza B virus NS1protein in-hibits conjugation of the interferon(IFN)-induced ubiquitin-like ISG15protein[J].EMBO J,2001,20(3):362-371.
- [29]Lai C,Struckhoff J J,Schneider J,et al.Mice lacking the ISG15E1enzyme UbE1L demonstrate increased susceptibility to both mouse-adapted and non-mouse-a-dapted influenza B virus infection[J].J Virol,2009,83(2):1147-1151.
- [30]Li L,Wang D,Jiang Y,et al.Crystal structure of hu-man ISG15in complex with influenza B virus NS1B[J].J Biol Chem,2011.
- [31]Zhao C,Hsiang T Y,Kuo R L,et al.ISG15conjuga-tion system targets the viral NS1protein in influenza A virus-infected cells[J].Proc Natl Acad Sci U S A,2010,107(5):2253-2258.
- [32]Durfee L A,Lyon N,Seo K,et al.The ISG15conju-gation system broadly targets newly synthesized pro-teins:implications for the antiviral function of ISG15[J].Mol Cell,2010,38(5):722-732.