Functional analysis of mutations conferring lamivudine resistance on hepatitis B virus

被引:44
作者
Ling, R [1 ]
Harrison, TJ [1 ]
机构
[1] UCL, Royal Free & Univ Coll, Sch Med, Dept Med, London NW3 2PF, England
关键词
D O I
10.1099/0022-1317-80-3-601
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:601 / 606
页数:6
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