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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Multiple influenza a (H3N2) mutations conferring resistance to neuraminidase inhibitors in a bone marrow transplant recipient
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Multiple influenza a (H3N2) mutations conferring resistance to neuraminidase inhibitors in a bone marrow transplant recipient

机译:多个甲型流感(H3N2)突变赋予骨髓移植受者神经氨酸酶抑制剂抗性

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Immunocompromised patients are predisposed to infections caused by influenza virus. Influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistant strains. Characterization of neuraminidase (NA) inhibitor (NAI)-resistant strains of influenza A virus is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified an NAI-resistant strain of influenza A (H3N2) virus in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy. In addition, a combination of a 4-amino-acid deletion at residues 245 to 248 (-245-248) accompanied by the E119V substitution occurred, causing resistance to or reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness, and transmission.
机译:免疫功能低下的患者容易感染流感病毒。流感病毒可能会导致相当高的发病率,包括这些患者的长期疾病和长时间的病毒脱落,从而促使使用更高剂量的药物并延长了抗病毒治疗的疗程。这种方法可能会促进耐药菌株的出现。甲型流感病毒对神经氨酸酶(NA)抑制剂(NAI)耐药菌株的表征对于证明耐药原因至关重要。在这项研究中,我们使用定量实时PCR和传统的Sanger测序技术,在免疫受损的患者中鉴定了NAI耐药性A型流感病毒(H3N2)病毒。通过深层基因测序的深入分析显示,在长时间的抗病毒治疗期间,出现了多种已知的抗病毒抗药性标志物,包括NA蛋白中的瞬时R292K和Q136K取代以及持续的E119K(N2编号)取代。另外,在残基245-248(-245-248)上出现4-氨基酸缺失并伴有E119V取代的组合,引起了对NAI(oseltamivir,zanamivir和peramivir)的抑制或抑制。在联合抗病毒治疗期间,在病毒准种库中产生了抗性变体。需要更多的研究来了解耐药性突变,病毒适应性和传播之间的相互作用。

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