Stuyver L J, Locarnini S A, Lok A, Richman D D, Carman W F, Dienstag J L, Schinazi R F
Veterans Affairs Medical Center, Decatur, GA, USA.
Hepatology. 2001 Mar;33(3):751-7. doi: 10.1053/jhep.2001.22166.
There is currently no universally accepted numbering convention for the antiviral drug-related resistance mutations in the reverse transcriptase (rt) domain of the human hepatitis B virus (HBV) polymerase. The published inconsistencies have resulted from different HBV genotypes. A standardized numbering system for HBV polymerase is proposed. The new system is based on functional observations of HBV surface gene proteins (preS1, preS2, and HBsAg) and on the current convention used for human immunodeficiency virus type 1 (HIV-1) polymerase proteins (protease, rt, and integrase), in which the amino acid numbering restarts at the first codon position of each domain. The HBV polymerase protein can be divided into 4 domains (terminal protein, spacer, rt, ribonuclease H) and each of these can be numbered separately. In this proposal, the HBV rt domain starts with the highly conserved EDWGPCDEHG motif, contains 344 amino acids, and the lamivudine-related resistance mutations are found at amino acid rtL180M (previously amino acid 528, 526, 515, or 525) and rtM204V/I (previously 552, 550, 539, or 549). The new consensus rt domain numbering system is genotype independent and allows investigators to number any previously and newly discovered antiviral-related amino acid change in a standardized manner.
目前，对于人类乙型肝炎病毒（HBV）聚合酶逆转录酶（rt）结构域中与抗病毒药物相关的耐药性突变，尚无普遍接受的编号惯例。已发表的不一致结果源于不同的HBV基因型。本文提出了一种用于HBV聚合酶的标准化编号系统。新系统基于对HBV表面基因蛋白（preS1、preS2和HBsAg）的功能观察，以及目前用于1型人类免疫缺陷病毒（HIV-1）聚合酶蛋白（蛋白酶、rt和整合酶）的惯例，其中氨基酸编号在每个结构域的第一个密码子位置重新开始。HBV聚合酶蛋白可分为4个结构域（末端蛋白、间隔区、rt、核糖核酸酶H），每个结构域可单独编号。在本提议中，HBV rt结构域从高度保守的EDWGPCDEHG基序开始，包含344个氨基酸，与拉米夫定相关的耐药性突变位于氨基酸rtL180M（以前为氨基酸528、526、515或525）和rtM204V/I（以前为552、550、539或549）。新的rt结构域共识编号系统不依赖于基因型，允许研究人员以标准化方式对任何先前和新发现的与抗病毒相关的氨基酸变化进行编号。
