Biological impacts of "hot-spot" mutations of hepatitis B virus X proteins are genotype B and C differentiated
Biological impacts of "hot-spot" mutations of hepatitis B virus X proteins are genotype B and C differentiated作者机构:Research Center of Molecular Medicine Fujian Medical University Fuzhou 350004 Fujian Province China Centre for the Study of Liver Disease and Department of Surgery The University of Hong Kong Pokfulam Hong Kong China
出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))
年 卷 期:2005年第11卷第30期
页 面:4703-4708页
核心收录:
学科分类:1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学]
基 金:Supported by the Foundation for the Author of National Excellent Doctoral Dissertation of PR China No. 200359Fujian Natural Science Key Foundation No 2002F005Fujian Science and Technology Innovation Foundation for Young Scientists No.2001J058
主 题:Hepatitis B virus Genotype X gene Mutation
摘 要:AIM: To investigate the biological impacts of hot-spot mutations on genotype B and C HBV X proteins (HBx).METHODS: Five types of hot-spot mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I,I127T+K130M+V131I, or K130M+V131I+F132Y, respectively,were generated by means of site-directed *** evaluate the anti-proliferative effects, HBx or related mutants expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity,and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples ***: As compared to standard genotype B HBx,mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity,compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity,while the mutants of I127T and I127T+K130M+V131I showed no ***: Hot-spot mutations affect the antiproliferation and transactivation activities of genotype B and/or C HBx, and the