He Jin-Yang, Zhu Yu-Tong, Yang Rui-Yi, Feng Li-Ling, Guo Xing-Bo, Zhang Feng-Xue, Chen Hong-Shan
Tropical Medicine Institute of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
World J Gastroenterol. 2005 Jul 21;11(27):4261-7. doi: 10.3748/wjg.v11.i27.4261.
To observe the Lamivudine resistance character of a DHBV strain in vitro and in vivo, and to analyze if the Lamivudine resistance character is caused by gene mutation or by abnormity of the Lamivudine metabolism.
Congenitally DHBV-negative Guangdong brown ducks and duck embryo liver cells were respectively taken as animal and cell model. The Lamivudine-susceptive DHBV and Lamivudine-resistant DHBV (LRDHBV) were infected and Lamivudine was administrated according to the divided groups. The changes of DHBV quantity in the animal and cell model were tested. Three Lamivudine-resistant and two Lamivudine-susceptive DHBV complete genomes were successfully amplified, sequenced and then submitted to GenBank. All the DHBV complete sequences in the GenBank at present were taken to align with the three LRDHBV to analyze the mutational points related to the Lamivudine-resistant mutation.
Both the animal and cell model showed that the large and the small dosage Lamivudine have no significant inhibitory effect on the LRDHBV. Five sequences of DHBV complete genomes were successfully cloned. The GenBank accession numbers of the three sequences of LRDHBV are AY521226, AY521227, and AY433937. The two strains of Lamivudine-susceptive DHBV are AY392760 and AY536371. The correlated mutational points are KorR86Q and AorE591T in the P protein.
The Lamivudine resistance character of this DHBV strain is caused by genome mutation; the related mutational points are KorR86Q and AorE591T and have no relations with the YMDD motif mutation.
观察一株鸭乙肝病毒（DHBV）体外及体内对拉米夫定的耐药特性，并分析其耐药特性是由基因突变还是拉米夫定代谢异常所致。
以先天性DHBV阴性的广东麻鸭和鸭胚肝细胞分别作为动物和细胞模型。感染对拉米夫定敏感的DHBV和对拉米夫定耐药的DHBV（LRDHBV），并按分组给予拉米夫定。检测动物和细胞模型中DHBV数量的变化。成功扩增、测序3株对拉米夫定耐药和2株对拉米夫定敏感的DHBV全基因组，然后提交至GenBank。将GenBank中目前所有的DHBV全序列与3株LRDHBV进行比对，分析与拉米夫定耐药突变相关的突变位点。
动物和细胞模型均显示，大剂量和小剂量拉米夫定对LRDHBV均无显著抑制作用。成功克隆了5个DHBV全基因组序列。3株LRDHBV序列的GenBank登录号分别为AY521226、AY521227和AY433937。2株对拉米夫定敏感的DHBV分别为AY392760和AY536371。相关突变位点为P蛋白中的KorR86Q和AorE591T。
该DHBV株的拉米夫定耐药特性是由基因组突变引起的；相关突变位点为KorR86Q和AorE591T，与YMDD基序突变无关。
