Map of the CMV DNA polymerase gene (UL54 or pol). Most of the UL54 mutations occur within the cluster of conserved regions of homology (Exo I through III and polymerization domains I through VII). Mutations conferring ganciclovir (GCV) and cidofovir (CDV) cross-resistance are most commonly found within the exonuclease domains and polymerization region V. Mutations conferring resistance to foscarnet (FOS) are located in the δC/Exo III domains and polymerization II and III domains. FOS, GCV, and valganciclovir cross-resistance mutations are located in polymerization regions VI and III. Mutations conferring resistance to all 4 drugs (FOS, GCV, valganciclovir, and CDV) are located in Exo III domains and polymerization regions III, VII, and V, and those conferring resistance to only CDV are in polymerization region III. (A) Functional regions of the DNA polymerase. (B) UL54 mutations with corresponding antiviral resistance profiles. (C) Codons corresponding to functional DNA polymerase regions and UL54 mutations. Reprinted from Lurain and Chou⁶⁹  with permission.