TY - JOUR
T1 - Frequency of UL97 Phosphotransferase Mutations Related to Ganciclovir Resistance in Clinical Cytomegalovirus Isolates
AU - Chou, Sunwen
AU - Guentzel, Susan
AU - Michels, Kendall R.
AU - Miner, Richard C.
AU - Drew, W. Lawrence
N1 - Funding Information:
Received 9 January 1995; revised 3 March 1995. Presented in part: Fifth International Cytomegalovirus Conference, Stockholm, May 1995. Financial support: Department of Veterans Affairs. Reprints or correspondence: Dr. Sunwen Chou, VA Medical Center 11IF, 3710 S.W. US Veterans Hospital Rd., Portland OR 97201.
PY - 1995/7
Y1 - 1995/7
N2 - Cytomegalovirus (CMV) isolates from subjects who received ganciclovir therapy were tested for susceptibility to ganciclovir by a plaque reduction assay. Results were correlated with restriction enzyme and sequence analysis of the CMV UL97 phosphotransferase gene. Of the 30 isolates, 20 had one or more mutations in UL97 affecting amino acid encoding at codons 460,520, or 591-596. All 20 were resistant to ganciclovir, with an IC50 of >6.0 µM (range, 6.7-50.0). The remaining 10 isolates had no mutations at these loci; 8 were susceptible to ganciclovir while the other 2 were borderline resistant (IC50s, 6.6 and 7.2 µM). None of 40 control CMV isolates from untreated infjects contained any amino acid changes at these loci. The three most common mutations at codons 460, 594, and 595 were detected by restriction digest analysis in 16 (80%) of 20 isolates and in 16 (73%) of 22 isolates with ganciclovir IC50s >6.0 µM. These results indicate that the majority of ganciclovir-resistant clinical isolates contain diagnostically useful mutations in UL97.
AB - Cytomegalovirus (CMV) isolates from subjects who received ganciclovir therapy were tested for susceptibility to ganciclovir by a plaque reduction assay. Results were correlated with restriction enzyme and sequence analysis of the CMV UL97 phosphotransferase gene. Of the 30 isolates, 20 had one or more mutations in UL97 affecting amino acid encoding at codons 460,520, or 591-596. All 20 were resistant to ganciclovir, with an IC50 of >6.0 µM (range, 6.7-50.0). The remaining 10 isolates had no mutations at these loci; 8 were susceptible to ganciclovir while the other 2 were borderline resistant (IC50s, 6.6 and 7.2 µM). None of 40 control CMV isolates from untreated infjects contained any amino acid changes at these loci. The three most common mutations at codons 460, 594, and 595 were detected by restriction digest analysis in 16 (80%) of 20 isolates and in 16 (73%) of 22 isolates with ganciclovir IC50s >6.0 µM. These results indicate that the majority of ganciclovir-resistant clinical isolates contain diagnostically useful mutations in UL97.
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U2 - 10.1093/infdis/172.1.239
DO - 10.1093/infdis/172.1.239
M3 - Article
C2 - 7797920
AN - SCOPUS:0029061548
SN - 0022-1899
VL - 172
SP - 239
EP - 242
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -