Codex_V5

Contrasting drug resistance phenotypes resulting from cytomegalovirus DNA polymerase mutations at the same exonuclease locus.

Abstract: The resistance phenotypes of mutations I521T and P522A are as predicted from the known mutation P522S, but divergent results with P522L indicate that different amino acid substitutions at the same position may not have the same effect on drug resistance. New mutations must be individually validated for proper interpretation of genotypic resistance testing.

Mutant	Gene	Virus	Antiviral	EC50 ratio	Phenotype
I521T	UL54	Human betaherpesvirus 5	Ganciclovir	2.10	Low level resistance
I521T	UL54	Human betaherpesvirus 5	Cidofovir	5.10	High level resistance
I521T	UL54	Human betaherpesvirus 5	Foscarnet	0.80	No resistance
P522A	UL54	Human betaherpesvirus 5	Ganciclovir	3.00	Intermediate level resistance
P522A	UL54	Human betaherpesvirus 5	Cidofovir	4.10	Intermediate level resistance
P522A	UL54	Human betaherpesvirus 5	Foscarnet	1.00	No resistance
P522L	UL54	Human betaherpesvirus 5			Natural polymorphism