Nedyalkova Marina S, Hayden Frederick G, Webster Robert G, Gubareva Larisa V
Department of Internal Medicine, Division of Epidemiology and Virology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
J Infect Dis. 2002 Mar 1;185(5):591-8. doi: 10.1086/339358. Epub 2002 Feb 14.
With the use of neuraminidase (NA) inhibitors (BCX-1812, oseltamivir, or zanamivir), drug-resistant variants of influenza A viruses were generated that lacked characteristic markers of resistance, such as substitutions in the NA active center or in the hemagglutinin. Drug resistance was associated with the accumulation of defective (Delta) RNA segments encoding NA. This phenomenon could be explained by reduced dependence of the virus on its NA activity. Analysis of the last isolates recovered from 11 volunteers, experimentally infected with influenza virus and treated with BCX-1812, revealed that they maintained full susceptibility to the drug in the NA inhibition assay (50% inhibitory concentration, 0.35-0.5 nM). The presence of DeltaRNA segments was detected in 1 of these isolates but was not found in the isolates recovered from placebo recipients (n = 8). Because of a lack of cell culture-based assays for susceptibility testing of human influenza viruses, detection of DeltaRNA segments should be considered an additional assay for monitoring of NA inhibitor resistance.
使用神经氨酸酶（NA）抑制剂（BCX - 1812、奥司他韦或扎那米韦）后，产生了甲型流感病毒的耐药变异体，这些变异体缺乏耐药的特征性标记，如NA活性中心或血凝素中的取代。耐药性与编码NA的缺陷（Delta）RNA片段的积累有关。这种现象可以通过病毒对其NA活性的依赖性降低来解释。对11名经实验感染流感病毒并用BCX - 1812治疗的志愿者最后分离出的毒株进行分析，结果显示它们在NA抑制试验中对该药物保持完全敏感性（50%抑制浓度，0.35 - 0.5 nM）。在其中1株分离物中检测到了DeltaRNA片段，但在从接受安慰剂的受试者中分离出的毒株（n = 8）中未发现。由于缺乏基于细胞培养的人类流感病毒敏感性检测方法，DeltaRNA片段的检测应被视为监测NA抑制剂耐药性的一种补充检测方法。
