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体外筛选出的赋予更昔洛韦抗性的新型巨细胞病毒UL54 DNA聚合酶基因突变

Novel Cytomegalovirus UL54 DNA Polymerase Gene Mutations Selected In Vitro That Confer Brincidofovir Resistance.

作者信息

Chou Sunwen, Ercolani Ronald J, Lanier E Randall

机构信息

Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA Research Service, VA Portland Health Care System, Portland, Oregon, USA

Research Service, VA Portland Health Care System, Portland, Oregon, USA.

出版信息

Antimicrob Agents Chemother. 2016 May 23;60(6):3845-8. doi: 10.1128/AAC.00214-16. Print 2016 Jun.

DOI:10.1128/AAC.00214-16
PMID:27044553
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4879386/
Abstract

Eight in vitro selection experiments under brincidofovir pressure elicited the known cytomegalovirus DNA polymerase amino acid substitutions N408K and V812L and the novel exonuclease domain substitutions D413Y, E303D, and E303G, which conferred ganciclovir and cidofovir resistance with 6- to 11-fold resistance to brincidofovir or 17-fold when E303G was combined with V812L. The new exonuclease domain I resistance mutations selected under brincidofovir pressure add to the single instance previously reported and show the expected patterns of cross-resistance.

摘要

在布林西多福韦压力下进行的八项体外筛选实验引发了已知的巨细胞病毒DNA聚合酶氨基酸取代N408K和V812L,以及新的核酸外切酶结构域取代D413Y、E303D和E303G,这些取代赋予了对更昔洛韦和西多福韦的耐药性,对布林西多福韦有6至11倍的耐药性,当E303G与V812L组合时则有17倍的耐药性。在布林西多福韦压力下选择的新的核酸外切酶结构域I耐药突变增加了先前报道的单一实例,并显示出预期的交叉耐药模式。

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