The Cys607→Tyr Change in the UL97 Phosphotransferase Confers Ganciclovir Resistance to Two Human Cytomegalovirus Strains Recovered from Two Immunocompromised Patients

Author:

Baldanti Fausto1,Underwood Mark R.2,Talarico Christine L.2,Simoncini Lavinia1,Sarasini Antonella1,Biron Karen K.2,Gerna Giuseppe1

Affiliation:

1. Servizio di Virologia, IRCCS Policlinico S. Matteo, 27100 Pavia, Italy,1 and

2. Department of Virology, Glaxo Wellcome Inc., Research Triangle Park, North Carolina 277092

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference25 articles.

1. Four dually resistant human cytomegalovirus strains from AIDS patients: single mutations in UL97 and UL54 open reading frames are responsible for ganciclovir- and foscarnet-specific resistance, respectively.;Baldanti F.;Scand. J. Infect. Dis. Suppl.,1995

2. A three-nucleotide deletion in the UL97 open reading frame is responsible for the ganciclovir resistance of a human cytomegalovirus clinical isolate

3. Baldanti F. M. Boeckh S. Chou C. Crumpacker S. Danner W. L. Drew D. Emanuel A. Erice W. D. Hardy and S. Spector. 1996. Drug resistance in cytomegalovirus: current knowledge and implications for patient management. J. Acquired Immune Defic. Syndr. Hum. Retrovirol. 12 (Suppl. 1) : S1–S22.

4. Single amino acid changes in the DNA polymerase confer foscarnet resistance and slow-growth phenotype, while mutations in the UL97-encoded phosphotransferase confer ganciclovir resistance in three double-resistant human cytomegalovirus strains recovered from patients with AIDS

5. Alpha-, beta- and gamma herpesviruses encode a putative phosphotranspherase.;Chee M. S.;J. Gen. Virol.,1989

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