Chou Sunwen, Wechel Laura C Van, Marousek Gail I
Oregon Health and Science University and Veterans Affairs Medical Center, Portland, OR, 97239, USA.
J Infect Dis. 2007 Jul 1;196(1):91-4. doi: 10.1086/518514. Epub 2007 May 17.
The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir (MBV) is undergoing clinical antiviral trials. Two clinical CMV isolates serially passaged in cell culture under MBV showed >20-fold increases in MBV resistance after the development of the UL97 mutation V353A in one of the isolates and of T409M in the other. Marker transfer studies confirmed that the V353A and T409M mutations conferred ~15-fold and ~80-fold increases, respectively, in MBV resistance without significantly affecting ganciclovir susceptibility. The 3 UL97 mutations now known to confer MBV resistance are located upstream of UL97 mutations linked to ganciclovir resistance, closer to kinase domains that are associated with adenosine triphosphate binding and phosphotransfer.
巨细胞病毒（CMV）UL97激酶抑制剂马里巴韦（MBV）正在进行抗病毒临床试验。在MBV作用下于细胞培养中连续传代的两株临床CMV分离株，其中一株出现UL97突变V353A，另一株出现T409M后，对MBV的耐药性增加了20倍以上。标记转移研究证实，V353A和T409M突变分别使MBV耐药性增加约15倍和约80倍，而对更昔洛韦敏感性无显著影响。目前已知的3种赋予MBV耐药性的UL97突变位于与更昔洛韦耐药性相关的UL97突变上游，更靠近与三磷酸腺苷结合和磷酸转移相关的激酶结构域。
