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局部注射西多福韦治疗复发性呼吸道乳头瘤病时出现病毒学失败与 HPV11 的遗传或表观遗传变化无关:连续分离株的全基因组比较。

Virological failure of intralesional cidofovir therapy in recurrent respiratory papillomatosis is not associated with genetic or epigenetic changes of HPV11: complete genome comparison of sequential isolates.

机构信息

Department of Medical Microbiology, University of Debrecen, H-4032 Debrecen, Nagyerdei krt. 98, Hungary.

出版信息

Antiviral Res. 2011 Nov;92(2):356-8. doi: 10.1016/j.antiviral.2011.09.007. Epub 2011 Sep 16.

Abstract

Five sequential human papillomavirus type 11 (HPV11) positive samples collected from an aggressive juvenile onset recurrent respiratory papillomatosis before, during and after intralesional cidofovir therapy leading to virological failure after initial response were analyzed. Sequencing of the complete genome as well as methylation analysis by bisulfate modification and sequencing of the long control region (LCR) were performed to seek for genetic and epigenetic changes as a possible background for therapy failure. Single-strand conformation polymorphism of E1, E2, E6, E7 and LCR was used to exclude the presence of multiple HPV11 infection. All five complete genomes were identical and all four E2 binding sites in the LCR were uniformly unmethylated in all five genomes. Thus the virological failure was not due to virological factors suggesting that cidofovir action may depend more heavily on the host.

摘要

对一名侵袭性儿童早发性复发性呼吸道乳头状瘤病患者,在病灶内使用更昔洛韦治疗导致病毒学失败之前、期间和之后采集的 5 份连续的 HPV11 阳性样本进行了分析。对完整基因组进行测序,对长控制区(LCR)进行亚硫酸氢盐修饰和测序,以寻找可能导致治疗失败的遗传和表观遗传变化。使用单链构象多态性分析 E1、E2、E6、E7 和 LCR,以排除存在多种 HPV11 感染的可能性。这 5 个完整基因组完全相同,LCR 中的所有 4 个 E2 结合位点在所有 5 个基因组中均均匀未甲基化。因此,病毒学失败不是由于病毒学因素所致,这表明更昔洛韦的作用可能更多地取决于宿主。

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