Genotypic characterization of human cytomegalovirus UL97 phosphotransferase natural polymorphism in the era of ganciclovir and maribavir

Genotypic characterization of human cytomegalovirus UL97 phosphotransferase natural polymorphism in the era of ganciclovir and maribavir
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DOI:
10.1016/j.antiviral.2011.04.015
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发表时间:
2011-07-01
期刊:
影响因子:
7.6
通讯作者:
Agut, Henri
Agut, Henri
中科院分区:
医学2区
文献类型:
--
作者:
Boutolleau, David;Burrel, Sonia;Agut, Henri

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迄今为止报道的人类巨细胞病毒(CMV)对更昔洛韦和马里巴韦耐药的分子机制主要依赖于UL97磷酸转移酶突变的存在。准确解释基因型抗病毒药物耐药试验结果需要明确区分耐药突变和自然株间序列变异。本工作的目的是扩大CMV UL97磷酸转移酶天然多态性的目录。对4株实验室菌株和35例未接受过抗巨细胞病毒治疗的患者的临床样本进行UL97基因全长序列分析。在核苷酸水平上,株间同源性为98%。在氨基酸水平上,十个以前从未描述过的自然多态性被鉴定出来。结合以往文献报道的结果,可以在更昔洛韦和马利巴韦时代建立新的UL97磷酸转移酶天然多态性图谱。(C), 2011 Elsevier B.V.版权所有
The molecular mechanisms of human cytomegalovirus (CMV) resistance to both ganciclovir and maribavir reported so far rely predominantly on the presence of mutations within UL97 phosphotransferase. The accurate interpretation of genotypic antiviral resistance assay results requires the clear distinction between resistance mutations and natural interstrain sequence variations. The objective of this work was to extend the catalog of CMV UL97 phosphotransferase natural polymorphism. The full-length UL97 gene sequence analysis from 4 laboratory strains and 35 clinical samples from patients who had not received any previous anti-CMV treatment was performed. At the nucleotide level, the interstrain identity was >98%. At the amino acid level, ten natural polymorphisms never previously described were identified. Together with all previous results reported in the literature, a new map of UL97 phosphotransferase natural polymorphism could be settled in the era of ganciclovir and maribavir. (C), 2011 Elsevier B.V. All rights reserved.