期刊
ANTIVIRAL RESEARCH
卷 193, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2021.105139
关键词
Cytomegalovirus; Genotypic resistance testing; Maribavir; Ganciclovir; UL97
资金
- National Institutes of Health [R01-AI116635]
Research has found that mutations in the UL97 gene of cytomegalovirus, specifically in the ATP binding region, may impact the resistance to ganciclovir and maribavir. Therefore, it is suggested to include testing of the UL97 ATP binding region in the standard diagnostic genotyping for better interpretation of drug resistance.
Because ganciclovir resistance mutations in the cytomegalovirus UL97 gene most commonly occur at codons 460, 520 and 590-607, diagnostic genotyping for drug resistance has often omitted the analysis of codons below 440. However, the UL97 kinase inhibitor maribavir selects for distinctive resistance mutations at codons 409 and 411, and ganciclovir/maribavir resistance mutations have also been described in the ATP binding region starting at codon 335. Expanded genotypic testing of UL97 codons 335-440 in 1535 clinical specimens disclosed 10 uncharacterized sequence variants that were phenotyped for ganciclovir and maribavir susceptibility. Notable findings included low-grade ganciclovir resistance conferred by amino acid substitutions K359N and E362D, decreased maribavir susceptibility of L348V, and maribavir hypersensitivity of V345I and E362D. Recently published substitutions F342Y and K359E/Q were also confirmed. The data indicate that mutations in the UL97 ATP binding region may arise in clinical specimens to affect the interpretation of ganciclovir and maribavir resistance. This region should now be included in the standard diagnostic genotyping of UL97, especially with the introduction of maribavir into therapeutic use.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据