Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study.
BMC Infect Dis
; 22(1): 568, 2022 Jun 22.
Article
en En
| MEDLINE
| ID: mdl-35733089
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Infecciones por Citomegalovirus
/
Farmacorresistencia Viral
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
BMC Infect Dis
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón