|
Basic Characteristics of Mutations
|
|
Mutation Site
|
A594V |
|
Mutation Site Sentence
|
While none of these patients' isolates demonstrated the 595 residue mutation, two (sen I-1 and sen I-2) contained nucleotide changes at position 1781 (C to T) and at position 1809 (C to G), which resulted in an alanine to valine substitution at position 594 and in cysteine to tryptophan substitution at position 603, respectively (Fig. 2 c and Table II). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
UL97 |
|
Standardized Encoding Gene
|
UL97
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HCMV-HIV Coinfeciton
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
7814623
|
|
Title
|
Mutations in human cytomegalovirus UL97 gene confer clinical resistance to ganciclovir and can be detected directly in patient plasma
|
|
Author
|
Wolf DG,Smith IL,Lee DJ,Freeman WR,Flores-Aguilar M,Spector SA
|
|
Journal
|
The Journal of clinical investigation
|
|
Journal Info
|
1995 Jan;95(1):257-63
|
|
Abstract
|
Specific mutations in the UL97 region of human cytomegalovirus (HCMV) have been found to confer resistance to laboratory-adapted strains subjected to ganciclovir selection. In this study, mutations in the UL97 region of HCMV isolates obtained from patients receiving ganciclovir therapy were examined to determine whether they would confer ganciclovir resistance, and if these mutations could be detected directly in the plasma of AIDS patients with progressive HCMV disease despite ganciclovir treatment. A single nucleotide change within a conserved region of UL97 was found in five resistant isolates, resulting in an amino acid substitution in residue 595: from leucine to phenylalanine in one, and from leucine to serine in four resistant isolates. A sixth resistant isolate demonstrated a single nucleotide change, leading to a threonine to isoleucine substitution in residue 659. The role of the 595 amino acid substitution in conferring ganciclovir resistance was confirmed by marker transfer experiments. In further studies, direct sequencing of HCMV DNA present in plasma obtained from persons with resistant viruses revealed the identical amino acid substitutions in plasma as those present in the cultured viruses. These findings indicate that clinical resistance to ganciclovir can result from specific point mutations in the UL97 gene, and that the emergence of the resistant genotype can be detected directly in patient plasma.
|
|
Sequence Data
|
-
|