Sequence evolution of putative cytotoxic T cell epitopes in NS3 region of hepatitis C virus  

作　　者：Hua-ZhangGuo YingYin Wen-LiangWang Chuan-ShanZhang TaoWang ZheWang JingZhang HongCheng Hai-TaoWang 

机构地区：[1]DepartmentofPathology,XijingHospital,FourthMilitaryMedicalUniversity,Xi'an710033,ShaanxiProvince,China [2]DepartmentofClinicalLaboratories,XijingHospital,FourthMilitaryMedicalUniversity,Xi'an710033,ShaanxiProvince,China [3]InstituteofMicrobiologyandEpidemiology,AcademyofMilitaryMedicalSciences,Beijing100071,China [4]DepartmentofPathology,XijingHospital,FourthMilitaryMedicalUniversity,Xi'an710033,ShaanxiProvince,China

出　　处：《World Journal of Gastroenterology》2004年第6期847-851,共5页世界胃肠病学杂志（英文版）

摘　　要：AIM:Quasispecies of hepatitis C virus (HCV) are the foundation for rapid sequence evolution of HCV to evade immune surveillance of hosts. The consensus sequence evolution of a segment of HCV NS3 region, which encompasses putative cytotoxic T cell epitopes,was evaluated.METHODS:Three male patients, infected with HCV through multiple transfusions,were identified from clinical symptoms and monitored by aminotransferase for 60 months.Blood samples taken at months 0, 32, and 60 were used for viral RNA extraction. A segment of HCV NS3 region was amplified from the RNA extraction by RT-PCR and subjected to subcloning and sequencing.HLA types of these three patients were determined using complement-dependent microlymphocytotoxic assay. CTL epitopes were predicted using MHC binding motifs.RESULTS:No patient had clinical symptoms or elevation of aspartate/alanine arninotransferase. Two patients showed positive HCV PCR results at all 3 time points. The other one showed a positive HCV PCR result only at month 0.A reported HLA-A2-restricted CTL epitope had no alteration in the HLA-A2-negative carrier over 60 months.In the HLA-A2-positive individuals, all the sequences from 0 month 0 showed an amber mutation on the initial codon of the epitope. Most changes of consensus sequences in the same patient occurred on predicted cytotoxic T cell epitopes.CONCLUSION:Amber mutation and changes of consensus sequence in HCV NS3 region may be related to viral immune escape.AIM:Quasispecies of hepatitis C virus (HCV) are the foundation for rapid sequence evolution of HCV to evade immune surveillance of hosts.The consensus sequence evolution of a segment of HCV NS3 region,which encompasses putative cytotoxic T cell epitopes,was evaluated. METHODS:Three male patients,infected with HCV through multiple transfusions,were identified from clinical symptoms and monitored by aminotransferase for 60 months.Blood samples taken at months 0,32,and 60 were used for viral RNA extraction.A segment of HCV NS3 region was amplified from the RNA extraction by RT-PCR and subjected to subcloning and sequencing.HLA types of these three patients were determined using complement-dependent microlymphocytotoxic assay.CTL epitopes were predicted using MHC binding motifs. RESULTS:No patient had clinical symptoms or elevation of aspartate/alanine aminotransferase.Two patients showed positive HCV PCR results at all 3 time points.The other one showed a positive HCV PCR result only at month 0.A reported HLA-A2-restricted CTL epitope had no alteration in the HLA-A2-negative carrier over 60 months.In the HLA- A2-positive individuals,all the sequences from 0 month 0 showed an amber mutation on the initial codon of the epitope.Most changes of consensus sequences in the same patient occurred on predicted cytotoxic T cell epitopes. CONCLUSION:Amber mutation and changes of consensus sequence in HCV NS3 region may be related to viral immune escape.

关 键 词：丙型肝炎病毒 细胞毒素 T细胞 抗原决定基 NS3区 逆转录聚合酶链反应 

分 类 号：R373.21[医药卫生—病原生物学]