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

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.