Characterization of viral genomic mutations in novel influenza A (H7N9)-infected patients: the association between oseltamivir-resistant variants and viral shedding duration
Characterization of viral genomic mutations in novel influenza A (H7N9)-infected patients: the association between oseltamivir-resistant variants and viral shedding duration
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新型甲型流感 (H7N9) 感染患者的病毒基因组突变特征：奥司他韦耐药变异与病毒脱落持续时间之间的关联
DOI：
10.1007/s11262-019-01678-8
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发表时间：
2019-07
期刊：
影响因子：
1.6
通讯作者：
Zheng Shufa
中科院分区：
文献类型：
--
作者：
Chen Renke;Zou Qi;a;Xie Guoliang;Yu Fei;Yang Xianzhi;Cao Lingyong;Huo Zhaoxia;Zheng Shufa
自2013年2月以来，中国东部地区出现了人感染新型甲型流感H7N9病毒的病例。检测病毒基因突变，分析患者的临床特征和病毒脱落时间与神经氨酸酶抑制剂（NAI）耐药相关，具有重要意义。收集31例H7N9住院患者临床标本，对NA、PB2、HA和M基因片段进行测序。在31例患者中，7例（22.6%）在NA中携带R292K突变，30例（96.8%），3例（9.7%）和5例（16.1%）在PB2中分别携带E627K、Q591K和D701N突变，2例（6.5%）在PB2中同时携带E627K和D701N突变。所有26例患者都携带Q226L突变，在HA的切割位点只有一个精氨酸(R)，在M2中有一个S31N突变。7例NA-R292K突变患者中，3例死亡，4例出院。NA-R292K突变型和NA-R292野生型患者在症状出现后开始使用奥司他韦治疗的天数无显著差异（中位天数，7 vs 6，P= 0.374）。在奥司他韦治疗后，NA-R292K突变型患者的病毒脱落持续时间明显长于NA-R292野生型患者（中位天数，10 vs 5，P= 0.022）。NA中R292K突变赋予潜在的奥司他韦耐药能力，导致病毒持续时间延长和预后不良，在感染患者的临床管理中应予以考虑。
Since February 2013, human infections with the novel influenza A H7N9 virus have occurred in eastern China. It is important to detect mutations in viral genes and analyze the clinical features of patients and viral shedding duration related to neuraminidase inhibitor (NAI) resistance. We collected clinical specimens from 31 hospitalized H7N9 patients and sequenced NA, PB2, HA, and M gene fragments. Of the 31 identified patients, 7 (22.6%) carried the R292K substitution in NA, 30 (96.8%), 3 (9.7%), and 5 (16.1%) carried E627K, Q591K, and D701N mutations in PB2, respectively, and 2 (6.5%) carried both E627K and D701N mutations in PB2. All 26 identified patients harbored Q226L mutations and possessed only a single arginine (R) at cleavage sites in the HA and a S31N mutation in M2. Among 7 NA-R292K mutated patients, 3 died and 4 were discharged. There was no significant difference in the days that patients started oseltamivir treatment after symptom onset between NA-R292K mutant and NA-R292 wild-type patients (median days, 7 vs 6,P= 0.374). NA-R292K mutant patients had a significantly longer duration of viral shedding than NA-R292 wild-type patients after oseltamivir treatment (median days, 10 vs 5,P= 0.022). The mutation of R292K in NA conferring the potential ability of oseltamivir resistance resulted in prolonged viral duration and poor outcome and should be taken into consideration in the clinical management of infected patients.
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