The Cys607-->Tyr change in the UL97 phosphotransferase confers ganciclovir resistance to two human cytomegalovirus strains recovered from two immunocompromised patients.
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.
Baldanti
F
F
Servizio di Virologia, IRCCS Policlinico S. Matteo, Pavia, Italy.
Underwood
M R
MR
Talarico
C L
CL
Simoncini
L
L
Sarasini
A
A
Biron
K K
KK
Gerna
G
G
D017088:AIDS-Related Opportunistic Infections / Q000821:virology*; D000998:Antiviral Agents / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004352:Drug Resistance, Microbial / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology*; D016027:Heart Transplantation; D006801:Humans; D016867:Immunocompromised Host; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*
D000998:Antiviral Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir