Human cytomegalovirus (HCMV) causes severe sequelae in immunocompromised hosts. Current antiviral therapies have serious adverse effects, with treatment in many clinical settings problematic, making new therapeutic approaches necessary. We examined the in vitro efficacy of small interfering RNAs (siRNAs) targeting the HCMV gene transcripts UL54 (DNA polymerase), UL97 (protein kinase) and UL122/...

Antiviral susceptibilities to ganciclovir, foscarnet, and cidofovir and sequencing of UL97 and DNA polymerase were done on 23 cytomegalovirus (CMV) isolates from 10 immunocompromised persons with end-organ CMV disease who were treated with ganciclovir alone or ganciclovir followed by foscarnet. Screening of UL97 for ganciclovir resistance mutations was done by restriction digest analysis. Of 14...

Human cytomegalovirus (CMV) remains the most common infection affecting organ transplant recipients. Despite advances in the prophylaxis and acute treatment of CMV, it remains an important pathogen affecting the short- and long-term clinical outcome of solid organ transplant recipient. The emergence of CMV resistance in a patient reduces the clinical efficacy of antiviral therapy, complicates t...

Human cytomegalovirus (CMV) remains the most common infection affecting organ transplant recipients. Despite advances in the prophylaxis and acute treatment of CMV, it remains an important pathogen affecting the short- and long-term clinical outcome of solid organ transplant recipient. The emergence of CMV resistance in a patient reduces the clinical efficacy of antiviral therapy, complicates t...

BACKGROUND The development of infections with ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) remains a serious problem in recipients of stem cell or organ transplants. Nearly all GCV-resistant clinical isolates have mutations in the viral UL97 gene. The rapid detection of GCV-resistant HCMV infections is necessary and the relative proportions of wild-type and mutant strains are predic...

BACKGROUND The human cytomegalovirus (HCMV) DNA polymerase is composed of the UL54 catalytic subunit and the UL44 accessory protein. UL44 increases the processivity of polymerase along the DNA template during replication and, incidentally, is a substrate for the UL97 phosphotransferase. The molecular mechanisms of HCMV resistance to antiviral drugs interfering with viral DNA synthesis reported ...

Most ganciclovir (GCV)-resistant cytomegalovirus (CMV) isolates contain UL97 gene mutations at codon 460 or 520 or between codons 590 and 607, where an increasing variety of mutations have been detected, including deletions. To determine their phenotypic effect, 9 UL97 mutations not previously studied were transferred to drug-sensitive laboratory CMV strains that contained unique restriction si...

The UL97-encoded protein kinase (pUL97) of human cytomegalovirus (HCMV) plays a critical role in the control of virus replication. Deletion of the UL97 gene results in a drastic reduction in the replication efficiency. Although the exact function of pUL97 remains unclear and its sensitivity to specific inhibitors is speculative, protein kinase inhibitors of the indolocarbazole class are effecti...