|
Basic Characteristics of Mutations
|
|
Mutation Site
|
A427S |
|
Mutation Site Sentence
|
Most of the unknown variants in Table 2 were selected for recombinant phenotyping, excluding those encountered as minority subpopulations in single samples (P385S, T398A, A427S) or mixed readouts at polymorphic codons (A427G), without available re-sequencing data. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
UL97 |
|
Standardized Encoding Gene
|
UL97
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
AD169
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Cytomegalovirus infections
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
34273445
|
|
Title
|
Ganciclovir and maribavir susceptibility phenotypes of cytomegalovirus UL97 ATP binding region mutations detected by expanded genotypic testing
|
|
Author
|
Chou S,Watters M,Sinha R,Kleiboeker S
|
|
Journal
|
Antiviral research
|
|
Journal Info
|
2021 Sep;193:105139
|
|
Abstract
|
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.
|
|
Sequence Data
|
-
|