HCVF蛋白和负性共刺激分子2B4与慢性HCV感染的关联研究  

Association between F protein and negative costimulatory molecule 2B4 in chronic HCV infection

作　　者：石丽萍[1] 李森森 肖雯[3] 裴家平 季晓伟[1] 蒋龙凤[4] 王长军[3] 邓小昭[1,3] 张琪[3] 韩一芳[3] 张锦海[3] 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(Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjiag 210029, China;Department of Microbial and Biochemical Pharmacy, School of Life Science and Technology, China Pharnuweutical University, Nanfing 210009, China;Institute of Disease Control and Prevention, Center for Disease Control and Prevention of Nanjing Command, Nanjing 210002, China;Department of Infection, the First Affiliated Hospital of Nanfing Medical University, Nanfing 210029, China)

机构地区：[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

出　　处：《中华疾病控制杂志》2018年第6期613-616,644,共5页Chinese Journal of Disease Control & Prevention

基　　金：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(interferonγ,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。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 se- creted 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 anti- body, 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 be- fore 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.

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 

分 类 号：R373.21[医药卫生—病原生物学]