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Review
. 2005 Mar;49(3):873-83.
doi: 10.1128/AAC.49.3.873-883.2005.

Human cytomegalovirus resistance to antiviral drugs

C Gilbert  1 , G Boivin
Affiliations
Review

Human cytomegalovirus resistance to antiviral drugs

C Gilbert et al. Antimicrob Agents Chemother. 2005 Mar.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Mechanisms of action of systemic antivirals approved for treatment of CMV infections. GCV and CDV, once phosphorylated, compete with dNTPs for the binding site on the DNA pol (A) and are incorporated into HCMV DNA (B), thus inhibiting viral DNA replication. FOS directly inhibits viral DNA replication by blocking the pyrophosphate (ppi) binding site (C), thus preventing ppi cleavage from incoming dNTPs and subsequent incorporation of the nucleotide into viral DNA. MP, DP, and TP, monophosphate, diphosphate, and triphosphate, respectively.
FIG. 2.
FIG. 2.
HCMV UL97 mutations conferring GCV resistance. HCMV UL97 conserved regions are represented by shaded boxes. The numbers under the boxes indicate the positions (codon numbers) of these conserved regions (58). Vertical bars indicate the presence of amino acid substitutions, while the hatched box indicates a region (codons 590 to 607) in which diverse codon deletions (from 1 to 17 codons) have been reported. Other mutations potentially associated with GCV resistance have been described at codons 466 and 521, but no susceptibility testing results were available (20, 44). *, the position of the UL97 mutation (codon 397) involved in maribavir (1263W94) resistance (14).
FIG. 3.
FIG. 3.
HCMV DNA polymerase (UL54) mutations conferring resistance to antivirals. HCMV DNA pol conserved regions are represented by shaded boxes. Numbers under and over the boxes indicate the positions (codon numbers) of these conserved regions (9, 16, 78, 115, 138). Vertical bars indicate the positions of mutations that have been associated with drug resistance. Other mutations (at codons 304, 393, 406, 521, 691, 695, 737, 751, 830, 834, 841, 961, and 972) potentially associated with drug resistance have been reported, but the presence in the same isolate of other known UL54 resistance mutations or the lack of phenotypic evaluation have precluded the ability to make an association with drug resistance (23, 26, 44, 49, 75, 112, 116). Note that resistant strains containing reported mutations were not necessarily tested for all antivirals listed. Dashed lines indicate that independent marker transfer experiments (codons 781 and 802) or substitutions by different amino acids (codon 756) have resulted in discrepant results.
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References

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