Chou Sunwen, Marousek Gail, Li Shaobing, Weinberg Adriana
Division of Infectious Diseases, Oregon Health and Science University, VA Medical Center, Portland, OR 97239, United States.
J Clin Virol. 2008 Sep;43(1):107-9. doi: 10.1016/j.jcv.2008.04.005. Epub 2008 May 27.
Diverse mutations in the cytomegalovirus (CMV) DNA polymerase (pol) gene confer resistance to one or more of the antiviral drugs ganciclovir, foscarnet or cidofovir. The levels of resistance conferred by specific mutations are variable, ranging from insignificant resistance to triple-drug resistance.
Three pol mutations, I521T, P522A and P522L, detected in patients who received antiviral therapy for CMV infection, were studied by recombinant phenotyping to characterize their associated drug resistance.
The individual mutations were transferred by homologous recombination into a reference CMV strain modified with a reporter gene and the drug concentrations required to reduce the reporter signal by 50% (IC50) were determined.
The mutations I521T and P522A each conferred 3- to 4-fold increases in IC50 to both ganciclovir and cidofovir, while mutation P522L conferred no significant resistance to either drug. None of these mutations conferred foscarnet resistance.
The resistance phenotypes of mutations I521T and P522A are as predicted from the known mutation P522S, but divergent results with P522L indicate that different amino acid substitutions at the same position may not have the same effect on drug resistance. New mutations must be individually validated for proper interpretation of genotypic resistance testing.
巨细胞病毒（CMV）DNA聚合酶（pol）基因中的多种突变可赋予对一种或多种抗病毒药物更昔洛韦、膦甲酸钠或西多福韦的耐药性。特定突变所赋予的耐药水平各不相同，从微不足道的耐药到三重耐药。
对在接受CMV感染抗病毒治疗的患者中检测到的三种pol突变I521T、P522A和P522L进行重组表型分析，以表征其相关的耐药性。
通过同源重组将各个突变转移到用报告基因修饰的参考CMV菌株中，并确定使报告信号降低50%（IC50）所需的药物浓度。
I521T和P522A突变使更昔洛韦和西多福韦的IC50均增加3至4倍，而P522L突变对这两种药物均无明显耐药性。这些突变均未赋予膦甲酸钠耐药性。
I521T和P522A突变的耐药表型与已知的P522S突变预测结果一致，但P522L的不同结果表明同一位置的不同氨基酸取代对耐药性的影响可能不同。必须对新突变进行单独验证，以便正确解释基因型耐药性检测结果。
