丙型肝炎炎症发生与细胞信号通路异常
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摘要
丙型肝炎病毒(hepatitis C virus,HCV)感染是引起慢性丙型肝炎的直接原因,炎症的持续发生会导致肝纤维化、硬化甚至是肝癌的出现。炎症发生通常与细胞信号通路异常相关,病毒感染后病毒蛋白干扰宿主细胞正常的信号转导途径,使得促炎和炎症相关分子异常表达,导致炎症的发生。了解HCV感染后炎症发生的分子机制将有助于防止丙型肝炎炎症的恶化,为临床抗病毒治疗提供参考。
HCV infection is the cause of chronic hepatitis C, and the subsequently sustained inflammation can result in liver fibrosis, cirrhosis and hepatic carcinoma. The occurrence of inflammation is usually associated with the abnormal cellular signal transduction. The interaction between viral proteins and the host proteins in signal transduction pathway may lead to unusual cellular expression of pro-inflammatory and inflammatory molecules. Understanding the molecular mechanism of hepatitis C inflammation is helpful for the prevention of hepatitis C inflammation, and provides the necessary basic data for its therapy.
HCV infection is the cause of chronic hepatitis C, and the subsequently sustained inflammation can result in liver fibrosis, cirrhosis and hepatic carcinoma. The occurrence of inflammation is usually associated with the abnormal cellular signal transduction. The interaction between viral proteins and the host proteins in signal transduction pathway may lead to unusual cellular expression of pro-inflammatory and inflammatory molecules. Understanding the molecular mechanism of hepatitis C inflammation is helpful for the prevention of hepatitis C inflammation, and provides the necessary basic data for its therapy.
引文
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[31]Zhang Z,Kim T,Bao M,et al.DDX1,DDX21,and DHX36 helicases form a complex with the adaptor molecule TRIF to sense ds RNA in dendritic cells.Immunity,2011,34:866-878
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[2]Zhao LJ,Wang W,Wang WB,et al.Involvement of ERK pathway in interferonαmediated antiviral activity against hepatitis C virus.Cytokine,2015,72:17-24
[3]Ibrahim MK,Salum GM,Bader El Din NG,et al.Transcriptional dysregulation of upstream signaling of IFN pathway in chronic HCV type 4 induced liver fibrosis.PLo S One,2016,11:e0154512
[4]Nasheri N,Ning Z,Figeys D,et al.Activity-based profiling of the proteasome pathway during hepatitis C virus infection.Proteomics,2015,15:3815-3825
[5]Shepard CW,Finelli L,Alter MJ.Global epidemiology of hepatitis C virus infection.Lancet Infect Dis,2005,5:558-567
[6]Wei L,Lok AS.Impact of new hepatitis C treatments in different regions of the world.Gastroenterology,2014,146:1145-1150
[7]Mohd Hanafiah K,Groeger J,Flaxman AD,et al.Global epidemiology of hepatitis C virus infection:new estimates of age-specific antibody to HCV seroprevalence.Hepatology,2013,57:1333-1342
[8]李杰,陈杰,庄辉.丙型肝炎的流行病学.实用肝脏病杂志.2012,15:379-383
[9]Poordad F,Mc Cone J,Bacon B,et al.Boceprevir for untreated chronic HCV genotype 1 infection.N Engl J Med,2011,364:1195-1206
[10]Jacobson IM,Mc Hutchison JG,Dusheiko G,et al.Telaprevir for previously untreated chronic hepatitis C virus infection.N Engl J Med,2011,364:2406-2416
[11]Fried MW,Buti M,Dore GJ,et al.Once-daily simeprevir(TMC435)with pegylated interferon and ribavirin in treatment-na?ve genotype 1 hepatitis C:The randomized PILLAR study.Hepatology,2013,58:1918-1929
[12]Sharon F,Michael Houghton,Stephen Coates,et al.Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults.Vaccine,2010,28:6367-6373
[13]Esumi M,Rikihisa T,Nishimura S,et al.Experimental vaccine activities of recombinant E1 and E2 glycoproteins and hypervariable region 1 peptides of hepatitis C virus in chimpanzees.Arch Virol,1999,144:973-980
[14]楚莉辉,李琦涵.丙型肝炎DNA疫苗研究进展.国外医学(病毒学分册),2004,5:141-145
[15]中华医学会传染病与寄生虫病学分会.丙型肝炎防治指南.中华传染病杂志,2004,22:131-136
[16]江家骥.丙型肝炎临床实践.人民卫生出版社,2010,84-85
[17]魏来.丙型肝炎临床诊断与治疗手册.北京科学出版社,2012,23-54
[18]曾劲伟,杨光,陈姝,等.佛山丙型肝炎病毒基因型及与病毒载量相关性的研究.中国卫生检验杂志,2013,23:3564-3573
[19]Gould TH,Grace K,Thorne G,et al.Effect of thoracic epidural anaesthesia on colonic blood flow.Br J Anaesth,2002,89:446-451
[20]Lee MH,Yang HI,Lu SN,et al.Hepatitis C virus seromarkers and subsequent risk of hepatocellular carcinoma:long-term predictors from a community-based cohort study.J Clin Oncol,2010,28:4587-4593
[21]王琰,朱新宇,王霞,等.太原地区丙型肝炎病毒基因分型及其临床意义.实用肝脏病杂志,2010,13:109-111
[22]杨海涛.慢性丙型肝炎患者HCV准种的变化及其意义分析.中国医药指南,2012,10:162-163
[23]韩碧华,周吉坤.丙型肝炎自然史.医学动物防制,2014,30:1347-1352
[24]赵兰娟,刘厚奇,朱诗应,等.丙型肝炎病毒致病新模式:包膜蛋白2对MAPK/ERK途径的激活.中国科学(C辑),2003,33:246-252
[25]Andrew M,Mark H.Hepatitis C virus NS5A:tales of a promiscuous protein.J Gen Virol,2004,85:2485-2502
[26]Qadri I,Iwahashi M,Capasso JM,et a1.Induced oxidative stress and activated expression of manganese superoxide dismutase during hepatitis C virus replication:role of JNK,p38 MAPK and AP-1.Biochem J,2004,378:919-928
[27]Joo M,Hahn YS,Kwon M,et al.Hepatitis C virus core protein suppresses NF-κB activation and cyclooxygenase-2 expression by direct interaction with IκB kinaseβ.J Virol,2005,79:7648-7657
[28]Kato N,Yoshida H,Ono-Nita SK,et al.Activation of intracellular signaling by hepatitis B and C viruses:C-viral core is the most potent signal inducer.Hepatology,2000,32:405-412
[29]Li Y,Boehning DF,Qian T,et al.Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+uniporter activity.FASEB J,2007,21:2474-2485
[30]Guozhong Gong,Gulam W,Rasheeda T,et al.Human hepatitis C virus NS5A protein alters intracellular calcium levels,induces oxidative stress,and activates STAT-3 and NF-κB.Proc Natl Acad Sci USA,2001,98:9599-9604
[31]Zhang Z,Kim T,Bao M,et al.DDX1,DDX21,and DHX36 helicases form a complex with the adaptor molecule TRIF to sense ds RNA in dendritic cells.Immunity,2011,34:866-878
[32]Borowski P,Schulze J,Resch K,et a1.Protein kinase C recognizes the protein kinase A—binding motif of nonstructural protein 3 of hepatitis C virus.J Biol Chem,1999,274:30722-30728
[33]李波,冯德云,文继舫,等.丙型肝炎病毒NS3蛋白促进人源肝细胞的增殖及其相关机制研究.生物化学与生物物理进展,2005,32:991-997