Novel DNA polymerase mutations conferring cytomegalovirus resistance: input of BAC-recombinant phenotyping and 3D model.

Long-term exposure to antiviral therapy in immunocompromised patients favors emergence of human cytomegalovirus (HCMV) resistance mutations. Two new UL54 DNA polymerase mutations (deletion of codon 524 and N408S substitution) identified in a kidney recipient and a bone marrow recipient respectively were characterized. Marker transfer experiment through recombination into a HCMV AD169 BAC demonstrated del524 and mutation N408S confer GCV and CDV resistance.

Eight flavonoids and their potential as inhibitors of human cytomegalovirus replication.

The drugs currently available for treatment of severe human cytomegalovirus (HCMV) infections suffer from many drawbacks, particularly toxicity, and potential teratogenicity contraindicating their use in target populations such as pregnant women. The emergence of drug-resistant strains is still a problem for disease management, particularly in immunosuppressed populations where antivirals are used for extended periods of time. The flavonoid family of drugs contains promising candidates as they have low toxicity and inhibit different targets to currently available antivirals.

Drug-resistant cytomegalovirus in transplant recipients: a French cohort study.

Objectives: Cytomegalovirus (CMV) drug resistance is a therapeutic challenge in the transplant setting. No longitudinal cohort studies of CMV resistance in a real-life setting have been published in the valganciclovir era. We report findings for a French multicentre prospective cohort of 346 patients enrolled at initial diagnosis of CMV infection (clinical trial registered at clinicaltrials.

Conserved domains and structure prediction of human cytomegalovirus UL27 protein.

Background: The human cytomegalovirus (HCMV) nuclear UL27 protein (pUL27) could be involved at the stage of nuclear egress. Maribavir is a new anti-HCMV drug that targets nuclear egress through direct inhibition of the HCMV serine-threonine kinase, UL97 protein (pUL97). Because maribavir-resistance-related mutations are observed in both proteins, pUL27 is thought to interfere with pUL97 activity; however, its mechanism of action remains unclear.

[cytomegalovirus; resistance; antiviral therapy; UL97 kinase; polymerase].

Antiviral resistance of cytomegalovirus strains is a growing problem in the transplant setting as it can concern 5% of patients with CMV replication. It is a consequence of the intensive and prolonged use of the three clinically approved inhibitors of the viral polymerase UL54, ganciclovir cidofovir and foscarnet. Resistance to ganciclovir can result from either mutations of the UL97 kinase, dispensable for its activation, which may appear within one month of therapy, or later from mutations in the UL54 viral polymerase, that can confer resistance to all antivirals.