Respiratory Virus Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MSC 3203 33 North Dr, Bethesda, MD 20892-3203, USA.
J Infect Dis. 2010 May 1;201(9):1397-403. doi: 10.1086/651610.
The overall impact of influenza virus infection in immunocompromised patients is largely unknown. Antigenic drift and genetic variations during prolonged influenza infection have been demonstrated. In this report we describe a multidrug-resistant H3N2 influenza virus isolated from an immunocompromised patient after 5 days of therapy.
Multiple nasal wash samples were collected from an infected patient, and viral isolates were characterized. Sensitivity to antiviral agents was evaluated. Fitness and transmissibility were assessed in ferrets and tissue culture.
An in-frame 4-amino acid deletion emerged in the neuraminidase (NA) gene of an H3N2 virus after 5 days of oseltamivir therapy. No other changes in the NA or hemagglutinin genes were noted. Drug sensitivity assays revealed resistance to oseltamivir (>10-fold increase in 50% inhibitory concentration [IC(50)]) and reduction in sensitivity to zanamivir (3-7-fold increase in IC(50) or 50% effective concentration). No change in fitness or transmissibility was observed.
An in-frame NA gene deletion was rapidly selected for in an immunocompromised patient, resulting in decreased sensitivity of the isolate to available NA inhibitors without a change in fitness or transmissibility. This finding has implications for our understanding of the emergence of antiviral resistance and treatment of patients with influenza A infection, especially those who are immunocompromised.
流感病毒感染对免疫功能低下患者的整体影响尚不清楚。在长时间的流感感染过程中，病毒发生了抗原漂移和基因变异。在本报告中，我们描述了一例免疫功能低下患者在接受 5 天治疗后分离出的一株多药耐药 H3N2 流感病毒。
从感染患者中采集多个鼻洗液样本，并对病毒分离株进行鉴定。评估了对抗病毒药物的敏感性。在雪貂和组织培养中评估了适应性和传染性。
在奥司他韦治疗 5 天后，一株 H3N2 病毒的神经氨酸酶（NA）基因中出现了 4 个氨基酸的框内缺失。NA 或血凝素基因没有其他变化。药物敏感性检测显示对奥司他韦耐药（50%抑制浓度[IC（50）]增加 10 倍以上）和对扎那米韦敏感性降低（IC（50）或 50%有效浓度增加 3-7 倍）。未观察到适应性或传染性的变化。
在免疫功能低下的患者中，NA 基因的框内缺失迅速被选择，导致分离株对现有 NA 抑制剂的敏感性降低，而适应性或传染性没有变化。这一发现对我们理解抗病毒耐药性的出现和治疗流感 A 感染患者，特别是免疫功能低下的患者具有重要意义。
