Characterization of human cytomegalovirus (HCMV) UL97 mutations found in a valganciclovir/oral ganciclovir prophylactic trial by use of a bacterial artificial chromosome containing the HCMV genome.
A method based on manipulation of the human cytomegalovirus genome in a bacterial artificial chromosome was developed to determine the role played by 6 UL97 mutations of unknown significance. These mutations were found in blood samples from solid-organ transplant recipients in a trial comparing valganciclovir and oral ganciclovir prophylaxis. Recombinant viruses containing UL97 mutations P405L, A427V, M550I, A582V, Y617H, and A674T were generated in a bacterial system. Viral stocks were subsequently reconstituted in human fibroblasts, and ganciclovir susceptibilities were tested using a plaque-reduction assay. All recombinant viruses containing these unknown mutations were found to be susceptible to ganciclovir.
Martin
Melanie
M
Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Quebec and Laval University, Quebec City, Canada.
Gilbert
Christian
C
Covington
Emma
E
Boivin
Guy
G
D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D022202:Chromosomes, Artificial, Bacterial; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016679:Genome, Viral; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011995:Recombination, Genetic; D014181:Transplantation Immunology; D000077562:Valganciclovir; D014779:Virus Replication
D000998:Antiviral Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D000077562:Valganciclovir; D015774:Ganciclovir