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HCVF蛋白和负性共刺激分子2B4与慢性HCV感染的关联研究
引用本文:石丽萍, 李森森, 肖雯, 裴家平, 季晓伟, 蒋龙凤, 王长军, 邓小昭, 张琪, 韩一芳, 张锦海. HCVF蛋白和负性共刺激分子2B4与慢性HCV感染的关联研究[J]. 中华疾病控制杂志, 2018, 22(6): 613-616,644. doi: 10.16462/j.cnki.zhjbkz.2018.06.017
作者姓名:石丽萍  李森森  肖雯  裴家平  季晓伟  蒋龙凤  王长军  邓小昭  张琪  韩一芳  张锦海
作者单位:1. 南京医科大学基础医学院生物化学与分子生物学系, 江苏 南京 210029;;;2. 中国药科大学生命科学与技术学院微生物与生化药学系, 江苏 南京 210009;;;3. 南京军区疾病预防控制中心疾病预防控制所, 江苏 南京 210002;;;4. 南京医科大学第一附属医院感染病科, 江苏 南京 210029
基金项目:国家自然科学基金(81573213);中国肝炎基金会天晴肝病研究基金(CFHPC20132071);江苏省自然科学基金(BK20151089,BK20161059,BL2013021)
摘    要:目的 探讨丙型肝炎病毒(hepatitis C virus,HCV)F蛋白的产生与负性共刺激分子2B4在慢性HCV感染中的关联性。方法 收集慢性HCV患者(chronic hepatitis patient,CHP)的血液样本,检测F抗体(F antibody,F-Ab)的阳性率并依据结果分成(HCV-F(+)组、HCV-F(-)组)两组,收集健康者的血液样本作为对照组;分离并培养外周血单核细胞(peripheral blood mononuclear cells,PBMCs),收集各孔细胞,酶联免疫吸附试验检测2B4抗体阻断前后白细胞介素4(interleukin 4,IL-4)、干扰素γ(interferon γ,IFN-γ)的表达水平。结果 2B4抗体阻断前,HCV患者PBMCs中IFN-γ和IL-4分泌水平均较健康组高(均有P<0.05),且HCV-F(-)组分泌IFN-γ水平高于HCV-F(+)组(F=1.908,P=0.020),而IL-4分泌水平低于HCV-F(+)组(F=1.342,P=0.009)。2B4抗体阻断后,健康组中IFN-γ和IL-4水平较阻断前均无统计学意义(均有P>0.05),CHP IFN-γ分泌水平较阻断前升高(F=1.214,P=0.003),且HCV-F(-)组升高程度高于HCV-F(+)组(F=1.434,P=0.009);而IL-4分泌水平较阻断前明显降低(F=1.505,P=0.015),且HCV-F(-)组降低程度低于HCV-F(+)组(F=1.444,P=0.032)。结论 在慢性HCV感染中,F蛋白的信号调控机制与负性共刺激分子2B4具有相关性。

关 键 词:丙型肝炎病毒F蛋白   负性共刺激分子2B4   丙型肝炎病毒感染
收稿时间:2017-12-27
修稿时间:2018-03-27

Association between F protein and negative costimulatory molecule 2B4 in chronic HCV infection
SHI Li-ping, LI Sen-sen, XIAO Wen, PEI Jia-ping, JI Xiao-wei, JIANG Long-feng, WANG Chang-jun, DENG Xiao-zhao, ZHANG Qi, HAN Yi-fang, ZHANG Jin-hai. Association between F protein and negative costimulatory molecule 2B4 in chronic HCV infection[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2018, 22(6): 613-616,644. doi: 10.16462/j.cnki.zhjbkz.2018.06.017
Authors:SHI Li-ping  LI Sen-sen  XIAO Wen  PEI Jia-ping  JI Xiao-wei  JIANG Long-feng  WANG Chang-jun  DENG Xiao-zhao  ZHANG Qi  HAN Yi-fang  ZHANG Jin-hai
Affiliation:1. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China;;;2. Department of Microbial and Biochemical Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China;;;3. Institute of Disease Control and Prevention, Center for Disease Control and Prevention of Nanjing Command, Nanjing 210002, China;;;4. Department of Infection, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Abstract:Objective To investigate the relationship between the production of hepatitis C virus (HCV) F protein and the negative costimulatory molecule 2B4 in chronic HCV infection. Methods The blood samples of chronic hepatitis patients (CHP) were collected and the positive rate of F antibody (F-Ab) was detected and divided into HCV-F(+) and HCV-F(-). Blood samples collected from healthy volunteers were used as control group. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured.The levels of interleukin 4 (IL-4),interferon γ (IFN-γ) before and after the blockade of 2B4 antibody were detected by enzyme-linkead immunosorbent assay. Results The levels of IFN-γ and IL-4 secreted in HCV patients were significantly higher than those in healthy controls (all P<0.05), and the level of IFN-γ secreted in HCV-F (-) group was significantly higher than that of HCV-F (+) group (F=1.908,P=0.020), while the level of IL-4 secretion was lower than that of HCV-F (+) group (F=1.342,P=0.009). After blocking with 2B4 antibody, the level of IFN-γ and IL-4 in healthy group had no significant change (all P>0.05). The level of IFN-γ in CHP group was significantly higher than that in the control group (F=1.214,P=0.003), and the levels in HCV-F (-) was higher than that of HCV-F (+) group (F=1.434,P=0.009). The levels of IL-4 were significantly lower than those before antibody block (F=1.505,P=0.015), and the levels in HCV-F (-) group were lower than those in HCV-F (+) group (F=1.444,P=0.032). Conclusions In chronic HCV infection, the signal regulation mechanism of F protein is correlated with negative costimulatory molecule 2B4.
Keywords:HCV F protein  Negative costimulatorymolecule 2B4  HCV infection
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