Chou S, Marousek G, Parenti D M, Gordon S M, LaVoy A G, Ross J G, Miner R C, Drew W L
Medical and Research Services, VA Medical Center, Portland, Oregon 97201, USA.
J Infect Dis. 1998 Aug;178(2):526-30. doi: 10.1086/515648.
Three human immunodeficiency virus-infected subjects with progressive cytomegalovirus (CMV) retinitis despite prolonged antiviral therapy had buffy coat CMV isolates that were resistant to both ganciclovir and foscarnet. Genetic analysis of the resistant isolates showed that each contained a well-known ganciclovir resistance mutation in the viral UL97 phosphotransferase sequence, as well as a mutation (Ala to Val at codon 809, V809) in conserved region III of the DNA polymerase (Pol) sequence. A segment of the Pol sequence from one of the clinical isolates was transferred to CMV laboratory strain AD169 by homologous recombination. The recombinant virus containing V809 showed 6.3-fold increased foscarnet resistance and 2.6-fold increased ganciclovir resistance. Occurrence of the V809 mutation in 3 unrelated cases suggests that it is a clinically significant viral genetic marker for foscarnet resistance and decreased susceptibility to ganciclovir.
三名人类免疫缺陷病毒感染患者，尽管接受了长时间的抗病毒治疗，但仍患有进行性巨细胞病毒（CMV）视网膜炎，其血沉棕黄层CMV分离株对更昔洛韦和膦甲酸钠均耐药。对耐药分离株的基因分析表明，每个分离株在病毒UL97磷酸转移酶序列中都含有一个众所周知的更昔洛韦耐药突变，以及DNA聚合酶（Pol）序列保守区域III中的一个突变（第809位密码子由丙氨酸变为缬氨酸，V809）。通过同源重组将来自其中一个临床分离株的一段Pol序列转移至CMV实验室菌株AD169。含有V809的重组病毒对膦甲酸钠的耐药性增加了6.3倍，对更昔洛韦的耐药性增加了2.6倍。在3例不相关病例中出现V809突变表明，它是膦甲酸钠耐药和对更昔洛韦敏感性降低的一个具有临床意义的病毒遗传标记。
