Ling R, Harrison T J
J Gen Virol. 1999 Mar;80 ( Pt 3):601-606. doi: 10.1099/0022-1317-80-3-601.
Two patterns of mutation are commonly observed in the polymerase gene of lamivudine [(-)2'-deoxy-3'-thiacytidine]-resistant hepatitis B virus (HBV). The M539I substitution in the conserved YMDD motif occurs independently of other changes, whereas the M539V substitution is associated with an additional upstream change (L515M). These mutations were introduced into a common background and their effects on HBV DNA replication and lamivudine resistance studied. The L515M and M539V mutations provided only partial resistance while the M539I mutation conferred a high degree of lamivudine resistance. The combination of the L515M and M539V mutations gave an intermediate level of replication competence, compared with either mutation alone, and increased resistance to lamivudine. This probably accounts for these two mutations always being observed together. The M539I mutation reduced replication competence.
在对拉米夫定[（-）-2'-脱氧-3'-硫代胞苷]耐药的乙型肝炎病毒（HBV）的聚合酶基因中，通常可观察到两种突变模式。保守的YMDD基序中的M539I替代独立于其他变化而发生，而M539V替代与一个额外的上游变化（L515M）相关。将这些突变引入到一个共同的背景中，并研究它们对HBV DNA复制和拉米夫定耐药性的影响。L515M和M539V突变仅提供部分耐药性，而M539I突变赋予高度的拉米夫定耐药性。与单独的任何一种突变相比，L515M和M539V突变的组合产生中等水平的复制能力，并增加对拉米夫定的耐药性。这可能解释了为何总是同时观察到这两种突变。M539I突变降低了复制能力。
