细胞内DNA识别受体与反转录病毒感染
摘要
反转录病毒可以通过模式识别受体触发一系列固有免疫应答反应,反转录病毒复制过程中会产生一系列的DNA中间体,包括RNA/DNA杂合体、单链DNA和双链DNA等,这些不同形式的DNA可被不同的DNA识别受体所识别,激活固有免疫应答反应,从而抑制反转录病毒的复制。环鸟苷酸-腺苷酸合成酶(c GAS)、γ干扰素诱导蛋白16(IFI16)及Ku70等细胞内DNA识别受体能够识别人类免疫缺陷病毒、成人T淋巴细胞病毒Ⅰ型、猴免疫缺陷病毒及鼠白血病病毒等反转录病毒的DNA中间体,与下游干扰素相关基因刺激因子(STING)相结合,诱导Ⅰ型干扰素(IFN)的产生及抗病毒免疫应答反应的启动。STING与TANK结合激酶1结合可以磷酸化和激活干扰素调节因子3,启动IFN-β和核因子κB的转录,从而抑制反转录病毒感染。本研究主要对反转录病毒感染过程中IFI16、c GAS、Ku70、STING及DEx D/H盒解螺旋酶41等细胞内DNA识别受体对反转录病毒感染的影响进行综述。
引文
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[2]KIGERL K A,DE RIVERO VACCARI J P,DIETRICH W D,et al.Pattern recognition receptors and central nervous system repair[J].Exp Neurol,2014,258:5-16.
[3]HRTLOVA A,ERTTMANN S F,RAFFI F A,et al.DNA damage primes the typeⅠinterferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity[J].Immunity,2015,42(2):332-343.
[4]BROWNE E P.An interleukin-1 beta-encoding retrovirus exhibits enhanced replication in vivo[J].J Virol,2015,89(1):155-164.
[5]ZHANG X,MA X,JING S,et al.Non-coding RNAs and retroviruses[J].Retrovirology,2018,15(1):20.
[6]POLETTI V,MAVILIO F.Interactions between retroviruses and the host cell genome[J].Mol Ther Methods Clin Dev,2017,8:31-41.
[7]HILDITCH L,TOWERS G J.A model for cofactor use during HIV-1 reverse transcription and nuclear entry[J].Curr Opin Virol,2014,4(2):32-36.
[8]VAN MONTFOORT N,OLAGNIER D,HISCOTT J.Unmasking immune sensing of retroviruses:interplay between innate sensors and host effectors[J].Cytokine Growth Factor Rev,2014,25(6):657-668.
[9]TIAN L,KIM M S,LI H,et al.Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid[J].Proc Natl Acad Sci USA,2018,115(3):507-512.
[10]ESPOSITO F,TRAMONTANO E.Current drugs targeting HIV-1integrase and reverse transcriptase-associated ribonuclease H activity:single and dual active site inhibitors[J].Antivir Chem Chemother,2014,23(4):129-144.
[11]ALTFELD M,GALE M J R.Innate immunity against HIV-1 infection[J].Nat Immunol,2015,16(6):554-562.
[12]王国庆,朱紫祥,曹伟军,等.RNA病毒阻断RIG-I样受体识别dsRNA机制研究进展[J].病毒学报,2014,30(6):704-712.
[13]LIU F,NIU Q,FAN X,et al.Priming and activation of inflammasome by canarypox virus vector ALVAC via the c GAS/IFI16-STING-typeⅠIFN pathway and AIM2 sensor[J].J Immunol,2017,199(9):3293-3305.
[14]LI W.Investigation of TypeⅠinterferon signaling in the cellular response and host defense[D].Sydney:University of Sydney School of Molecular Bioscience,2014.
[15]CHEN K,LIU J,CAO X T.Regulation of type I interferon signaling in immunity and inflammation:a comprehensive review[J].J Autoimmun,2017,83:1-11.
[16]CAI X,CHIU Y H,CHEN Z J.The c GAS-c GAMP-STING pathway of cytosolic DNA sensing and signaling[J].Mol Cell,2014,54(2):289-296.
[17]CHEN Q,SUN L,CHEN Z J.Regulation and function of the c GAS-STING pathway of cytosolic DNA sensing[J].Nat Immunol,2016,17(10):1142-1149.
[18]谢欣,王孝伟,刘俊义.免疫途径抗HIV信号通路:c GASSTING研究进展[J].国际药学研究杂志,2014,41(5):528-532.
[19]马玲玲,郭志祥,宋迪,等.c GAS通过调控固有免疫应答抑制HTLV-1在He La细胞中复制[J].中华微生物学和免疫学杂志,2017,37(11):822-826.
[20]JAKOBSEN M R,OLAGNIER D,HISCOTT J.Innate immune sensing of HIV-1 infection[J].Curr Opin HIV AIDS,2015,10(2):96-102.
[21]THOMPSON M R,SHARMA S,ATIANAND M,et al.Interferonγ-inducible protein(IFI)16 transcriptionally regulates typeⅠinterferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses[J].J Biol Chem,2014,289(34):23568-23581.
[22]NISSEN S K,HJEN J F,ANDERSEN K L D,et al.Innate DNA sensing is impaired in HIV patients and IFI16 expression correlates with chronic immune activation[J].Clin Exp Immunol,2014,177(1):295-309.
[23]许云龙.小鼠p200蛋白家族基因的表达模式[D].济南:山东大学,2014.
[24]STAVROU S,BLOUCH K,KOTLA S,et al.Nucleic acid recognition orchestrates the anti-viral response to retroviruses[J].Cell Host Microbe,2015,17(4):478-488.
[25]ZHANG X,BRANN T W,ZHOU M,et al.Ku70 is a novel cytosolic DNA sensor and induces type-ⅢIFN rather than Type-ⅠIFN[J].J Immunol,2011,186(8):4541-4545.
[26]SUI H,ZHOU M,IMAMICHI H,et al.STING is an essential mediator of the Ku70-mediated production of IFN-λin response to exogenous DNA[J].Sci Signal,2017,10(488):5054.
[27]WANG J,KANG L,SONG D,et al.Ku70 senses HTLV-1 DNA and modulates HTLV-1 replication[J].J Immunol,2017,199(7):2475-2482.
[28]郭若一,韩嫣,胡洁,等.胞质DNA受体及其对干扰素调控作用研究进展[J].国际免疫学杂志,2014,37(6):479-484.
[29]LEE K G,KIM S S,KUI L,et al.Bruton's tyrosine kinase phosphorylates DDX41 and activates its binding of ds DNA and STING to initiate type 1 interferon response[J].Cell Rep,2015,10(7):1055-1065.
[30]STAVROU S,BLOUCH K,KOTLA S,et al.Nucleic acid recognition orchestrates the anti-viral response to retroviruses[J].Cell Host Microbe,2015,17(4):478-488.
[31]SZE A,BELGNAOUI S M,LIN R,et al.Host restriction factor SAMHD1 limits human T-cell leukemia virus(HTLV-1)infection of primary monocytes via the innate immune sensor STING[J].Retrovirology,2014,11(Suppl 1):19.
[32]HERZNER A M,HAGMANN C A,GOLDECK M,et al.Sequencespecific activation of the DNA sensor c GAS by Y-form DNA structures as found in primary HIV-1 c DNA[J].Nat Immunol,2015,16(10):1025-1033.
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