Two HCMV proteins are implicated in antiviral resistance against these three drugs: pUL97 and pUL54. Specific mutations in pUL97 can cause reduced phosphorylation activity of this viral protein kinase. Thus, fewer monophosphorylated – and thus active – GCV can be synthesized, leading to antiviral resistance against GCV. About 90% of all GCV resistances are caused by such mutations in UL97. Mutations in pUL54 may have different effects leading to antiviral drug resistance: A. They can lead to decreased affinity to antiviral compounds. This resistance mechanism concerns GCV, CDV and FOS and may lead to multidrug resistance. B. Some mutations in pUL54 can increase the polymerase's exonuclease activity. This causes enhanced recognition of incorporated GCV and CDV. As a result, these dNTP analogues are excised more efficiently.