Codex_V5

Foscarnet resistance mutations mapping to atypical domains of the cytomegalovirus DNA polymerase gene.

Pubmed_id: 27940027
Journal: Antiviral research
Genbank_id: No known Genbank_id
Date: Feb 2017
Volume: 138
Issue: None
Pages: 57-60
Author(s): Chou S,

Abstract: Human cytomegalovirus UL54 DNA polymerase gene mutations that confer foscarnet resistance in clinical practice typically cluster in the amino terminal 2, palm and finger domains. Exposure to foscarnet in cell culture selected for mutations elsewhere in UL54, including amino acid substitutions S290R in the amino terminal 1 domain and E951D in the palm 2 domain. These are newly confirmed to confer foscarnet resistance and slightly decreased ganciclovir susceptibility. Other emergent substitutions N495K, T552N and T838A are known to confer foscarnet resistance, while additional ones Q783R and V798A only slightly affected susceptibility. An expanded set of domains is involved in foscarnet resistance and its genotypic diagnosis.

Mutations:

Mutant	Gene	Virus	Antiviral	EC50 ratio	Phenotype
S290R	UL54	Human betaherpesvirus 5	Cidofovir	1.30	No resistance
S290R	UL54	Human betaherpesvirus 5	Cidofovir	1.40	No resistance
S290R	UL54	Human betaherpesvirus 5	Foscarnet	2.20	Low level resistance
S290R	UL54	Human betaherpesvirus 5	Foscarnet	2.30	Low level resistance
S290R	UL54	Human betaherpesvirus 5	Ganciclovir	1.50	No resistance
S290R	UL54	Human betaherpesvirus 5	Ganciclovir	1.70	No resistance
K426E	UL54	Human betaherpesvirus 5	Cidofovir	1.00	No resistance
K426E	UL54	Human betaherpesvirus 5	Cidofovir	0.90	No resistance
K426E	UL54	Human betaherpesvirus 5	Foscarnet	1.10	No resistance
K426E	UL54	Human betaherpesvirus 5	Foscarnet	0.90	No resistance
K426E	UL54	Human betaherpesvirus 5	Ganciclovir	1.00	No resistance
K426E	UL54	Human betaherpesvirus 5	Ganciclovir	1.10	No resistance
N495K	UL54	Human betaherpesvirus 5	Cidofovir	1.20	No resistance
N495K	UL54	Human betaherpesvirus 5	Cidofovir	1.00	No resistance
N495K	UL54	Human betaherpesvirus 5	Foscarnet	2.50	Low level resistance
N495K	UL54	Human betaherpesvirus 5	Foscarnet	2.60	Low level resistance
N495K	UL54	Human betaherpesvirus 5	Ganciclovir	1.30	No resistance
N495K	UL54	Human betaherpesvirus 5	Ganciclovir	1.40	No resistance
T552N	UL54	Human betaherpesvirus 5	Cidofovir	1.00	No resistance
T552N	UL54	Human betaherpesvirus 5	Cidofovir	1.70	No resistance
T552N	UL54	Human betaherpesvirus 5	Foscarnet	2.50	Low level resistance
T552N	UL54	Human betaherpesvirus 5	Foscarnet	3.10	Intermediate level resistance
T552N	UL54	Human betaherpesvirus 5	Ganciclovir	1.80	No resistance
T552N	UL54	Human betaherpesvirus 5	Ganciclovir	2.60	Low level resistance
Q783R	UL54	Human betaherpesvirus 5	Cidofovir	0.90	No resistance
Q783R	UL54	Human betaherpesvirus 5	Foscarnet	1.70	No resistance
Q783R	UL54	Human betaherpesvirus 5	Ganciclovir	1.80	No resistance
Q783R	UL54	Human betaherpesvirus 5	Ganciclovir	1.30	No resistance
V798A	UL54	Human betaherpesvirus 5	Cidofovir	1.00	No resistance
V798A	UL54	Human betaherpesvirus 5	Cidofovir	1.10	No resistance
V798A	UL54	Human betaherpesvirus 5	Foscarnet	1.70	No resistance
V798A	UL54	Human betaherpesvirus 5	Foscarnet	1.80	No resistance
V798A	UL54	Human betaherpesvirus 5	Ganciclovir	1.50	No resistance
A809V	UL54	Human betaherpesvirus 5	Foscarnet	3.60	Intermediate level resistance
A809V	UL54	Human betaherpesvirus 5	Foscarnet	4.40	Intermediate level resistance
E951D	UL54	Human betaherpesvirus 5	Cidofovir	1.00	No resistance
E951D	UL54	Human betaherpesvirus 5	Cidofovir	1.20	No resistance
E951D	UL54	Human betaherpesvirus 5	Foscarnet	3.90	Intermediate level resistance
E951D	UL54	Human betaherpesvirus 5	Foscarnet	4.40	Intermediate level resistance
E951D	UL54	Human betaherpesvirus 5	Ganciclovir	2.20	Low level resistance
E951D	UL54	Human betaherpesvirus 5	Ganciclovir	1.80	No resistance
A987G	UL54	Human betaherpesvirus 5	Cidofovir	8.50	High level resistance
A987G	UL54	Human betaherpesvirus 5	Cidofovir	5.00	High level resistance
C592G	UL97	Human betaherpesvirus 5	Ganciclovir	3.00	Intermediate level resistance
C592G	UL97	Human betaherpesvirus 5	Ganciclovir	3.10	Intermediate level resistance

CHARMD

Comprehensive Herpesviruses Antiviral drug Resistance Mutation Database

Foscarnet resistance mutations mapping to atypical domains of the cytomegalovirus DNA polymerase gene.

Mutations: