Chou S, Guentzel S, Michels K R, Miner R C, Drew W L
Medical and Research Services, VA Medical Center, Portland, OR 97201, USA.
J Infect Dis. 1995 Jul;172(1):239-42. doi: 10.1093/infdis/172.1.239.
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 microM (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 microM). None of 40 control CMV isolates from untreated subjects 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 microM. These results indicate that the majority of ganciclovir-resistant clinical isolates contain diagnostically useful mutations in UL97.
通过蚀斑减少试验对接受更昔洛韦治疗的受试者的巨细胞病毒（CMV）分离株进行更昔洛韦敏感性检测。结果与CMV UL97磷酸转移酶基因的限制性内切酶分析和序列分析相关。在30株分离株中，20株在UL97中有一个或多个突变，影响460、520或591 - 596密码子处的氨基酸编码。所有20株对更昔洛韦耐药，IC50>6.0微摩尔（范围为6.7 - 50.0）。其余10株在这些位点无突变；8株对更昔洛韦敏感，另外2株为临界耐药（IC50分别为6.6和7.2微摩尔）。来自未治疗受试者的40株对照CMV分离株在这些位点均未出现任何氨基酸变化。通过限制性酶切分析在20株分离株中的16株（80%）以及IC50>6.0微摩尔的22株分离株中的16株（73%）中检测到460、594和595密码子处三种最常见的突变。这些结果表明，大多数耐更昔洛韦的临床分离株在UL97中含有具有诊断价值的突变。
