Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study

Yuka Torii, Kazuhiro Horiba, Jun ichi Kawada, Kazunori Haruta, Makoto Yamaguchi, Takako Suzuki, Hideko Uryu, Naoyuki Kashiwa, Keiji Goishi, Tomoo Ogi, Yoshinori Ito

研究成果: ジャーナルへの寄稿学術論文査読

9 被引用数 (Scopus)

抄録

Background: Congenital human cytomegalovirus (cCMV) infection can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Ganciclovir and valganciclovir (GCV/VGCV) improve long-term audiologic and neurodevelopmental outcomes for patients with cCMV infection; however, antiviral drug resistance has been documented in some cases. Long-read sequencing can be used for the detection of drug resistance mutations. The objective of this study was to develop full-length analysis of UL97 and UL54, target genes with mutations that confer GCV/VGCV resistance using long-read sequencing, and investigate drug resistance mutation in patients with cCMV infection. Methods: Drug resistance mutation analysis was retrospectively performed in 11 patients with cCMV infection treated with GCV/VGCV. UL97 and UL54 genes were amplified using blood DNA. The amplicons were sequenced using a long-read sequencer and aligned with the reference gene. Single nucleotide variants were detected and replaced with the reference sequence. The replaced sequence was submitted to a mutation resistance analyzer, which is an open platform for drug resistance mutations. Results: Two drug resistance mutations (UL54 V823A and UL97 A594V) were found in one patient. Both mutations emerged after 6 months of therapy, where viral load increased. Mutation rates subsided after cessation of GCV/VGCV treatment. Conclusions: Antiviral drug resistance can emerge in patients with cCMV receiving long-term therapy. Full-length analysis of UL97 and UL54 via long-read sequencing enabled the rapid and comprehensive detection of drug resistance mutations.

本文言語英語
論文番号568
ジャーナルBMC Infectious Diseases
22
1
DOI
出版ステータス出版済み - 12-2022
外部発表はい

All Science Journal Classification (ASJC) codes

  • 感染症

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