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The Cys607→Tyr Change in the UL97 Phosphotransferase Confers Ganciclovir Resistance to Two Human Cytomegalovirus Strains Recovered from Two Immunocompromised Patients
Author(s) -
Fausto Baldanti,
Mark Underwood,
Christine L. Talarico,
L. Simoncini,
Antonella Sarasini,
Karen K. Biron,
Giuseppe Gerna
Publication year - 1998
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.42.2.444
Subject(s) - ganciclovir , human cytomegalovirus , phosphotransferase , virology , recombinant dna , cytomegalovirus , strain (injury) , biology , betaherpesvirinae , pep group translocation , microbiology and biotechnology , herpesviridae , virus , phosphorylation , enzyme , gene , viral disease , biochemistry , phosphoenolpyruvate carboxykinase , anatomy
Two ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) strains recovered from an AIDS patient (strain VR4990) and a heart transplant recipient (strain VR5474) showed a Cys607→Tyr change in the UL97-encoded phosphotransferase. No amino acid substitutions were observed in the viral DNA polymerase. Marker transfer experiments showed marked reduction in GCV phosphorylation and drug susceptibility of the recombinant HCMV strain VR4990rec2-1-1. These results further extend the region of the carboxy-terminal domain of the UL97 phosphotransferase involved in GCV substrate recognition.

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