Maribavir sensitivity of cytomegalovirus isolates resistant to ganciclovir, cidofovir or foscarnet.
BACKGROUND
The cytomegalovirus (CMV) UL97 inhibitor drug maribavir (MBV) is undergoing clinical antiviral trials.


OBJECTIVE
To assess the MBV sensitivity of CMV strains and isolates containing mutations that confer resistance to current antiviral drugs ganciclovir, cidofovir or foscarnet.


METHODS
Resistant clinical isolates and laboratory strains containing UL97 and or UL54 DNA polymerase mutations were tested for sensitivity to all four drugs by standard plaque reduction assay and a reporter-based yield reduction assay. Sensitive control strains were also tested.


RESULTS
Eleven CMV strains or isolates resistant to GCV, four resistant to FOS and two resistant to CDV, were all sensitive to MBV. These viruses represent four UL97 mutations and three UL54 DNA polymerase mutations. The laboratory derived UL97 L397R mutant was highly MBV-resistant but remained sensitive to the other three drugs.


CONCLUSIONS
No cross-resistance has been detected between viruses resistant to MBV and those resistant to one or more of the current CMV antiviral drugs, consistent with differences in their mechanisms of action.
Drew
W Lawrence
WL
UCSF Mount Zion Medical Center, University of California, 1600 Divisadero Street, San Francisco, CA 94115, USA. lawrence.drew@clinlab.ucsfmedctr.org
Miner
Richard C
RC
Marousek
Gail I
GI
Chou
Sunwen
S
D000998:Antiviral Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral; D017245:Foscarnet / Q000494:pharmacology*; D015774:Ganciclovir / Q000494:pharmacology*; D006801:Humans; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000235:genetics; D012263:Ribonucleosides / Q000494:pharmacology*; D014764:Viral Proteins / Q000235:genetics; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
D000998:Antiviral Agents; D001562:Benzimidazoles; D000077404:Cidofovir; D003596:Cytosine; D004259:DNA-Directed DNA Polymerase; D017245:Foscarnet; D015774:Ganciclovir; D063065:Organophosphonates; D017853:Phosphotransferases (Alcohol Group Acceptor); D012263:Ribonucleosides; D014764:Viral Proteins; C109367:UL54 protein, Human herpesvirus 5; C075365:ganciclovir kinase; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole