Background: Human cytomegalovirus (HCMV) infections remain a major problem in immunocompromised patients. Three antiviral agents, ganciclovir (GCV), foscarnet (FOS) and cidofovir (CDV), are currently approved for the treatment of HCMV infections. They all target the viral DNA polymerase and are associated with significant side effects.
View Article and Find Full Text PDFUnlabelled: DNA polymerases of the Herpesviridae and bacteriophage RB69 belong to the α-like DNA polymerase family. In spite of similarities in structure and function, the RB69 enzyme is relatively resistant to foscarnet, requiring the mutation V478W in helix N to promote the closed conformation of the enzyme to make it susceptible to the antiviral. Here, we generated recombinant herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) mutants harboring the revertant in UL30 (W781V) and UL54 (W780V) DNA polymerases, respectively, to further investigate the impact of this tryptophan on antiviral drug susceptibility and viral replicative capacity.
View Article and Find Full Text PDFCytomegalovirus resistance to antivirals is a major problem in transplant recipients. We evaluated the impact of five mutations (A594V, L595F, and E655K in the UL97 gene and V526L and E756K in the UL54 gene), detected in a blood sample from a stem cell transplant recipient, on drug susceptibilities and replicative capacities of recombinant viruses.
View Article and Find Full Text PDFHuman cytomegalovirus (HCMV) resistance to antivirals is a major problem in immunocompromised patients. Drug resistance is characterized by phenotypic testing or genotypic analysis of the phosphotransferase (UL97) and DNA polymerase (UL54) genes. However, genotypic assays require further characterization of unknown mutations in the drug resistance phenotype.
View Article and Find Full Text PDFOn the basis of one case, the authors give the highlights on the various clinicopathological features of malignant gastric perforations. While medical imaging does not seem to contribute much in the positive diagnosis of such complications, it does remain essential to establish the local extension of the tumour process and thus to allow a better therapeutic management.
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