The effects of neuraminidase inhibitors on the release of oseltamivir‐sensitive and oseltamivir‐resistant influenza viruses from primary cultures of human tracheal epithelium
The effects of neuraminidase inhibitors on the release of oseltamivir‐sensitive and oseltamivir‐resistant influenza viruses from primary cultures of human tracheal epithelium
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DOI：
10.1002/jmv.23974
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发表时间：
2015-01
影响因子：
12.7
通讯作者：
M. Yamaya;L. Nadine;H. Kubo;Kousuke Saito;R. Saito;H. Nishimura
中科院分区：
文献类型：
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作者：
M. Yamaya;L. Nadine;H. Kubo;Kousuke Saito;R. Saito;H. Nishimura
明确神经氨酸酶抑制剂对流感病毒感染的影响可能为患者的治疗提供重要信息。神经氨酸酶抑制剂的作用已经使用各种方法进行了检查，包括从肾细胞释放病毒。然而，尚未研究神经氨酸酶抑制剂对保留原始组织功能的人气管上皮细胞原代培养物中病毒释放的影响。检查了神经氨酸酶抑制剂对大流行性流感病毒[A/Sendai-H/N 0633/2009（H1N1）pdm 09]和2008-2009年季节分离的季节性流感病毒[A/Sendai-H/216/2009（H1N1）]复制的影响。通过用大流行性或季节性流感病毒感染气管细胞来产生病毒储备液。四种类型的抑制剂（奥司他韦、扎那米韦、拉尼米韦和帕拉米韦）降低了大流行病毒滴度和细胞因子白细胞介素-6和肿瘤坏死因子-α在上清液中的浓度以及细胞中的病毒RNA。然而，奥司他韦并没有降低季节性病毒滴度、细胞因子浓度和病毒RNA，奥司他韦对季节性病毒神经氨酸酶活性的50%抑制浓度（IC 50）比大流行性流感病毒高300倍。季节性流感病毒具有奥司他韦耐药基因型。神经氨酸酶抑制剂对季节性流感病毒的IC 50值的大小与对病毒释放的抑制作用的大小呈负相关。这些用于测量人气管上皮原代培养物中病毒和炎症细胞因子释放的方法可能会提供有关神经氨酸酶抑制剂对流感病毒影响的有用信息。J. Med. Virol. 87：25-34，2015.© 2014 Wiley Periodicals，Inc.
Defining the effects of neuraminidase inhibitors on influenza virus infection may provide important information for the treatment of patients. The effects of neuraminidase inhibitors have been examined using various methods, including viral release from kidney cells. However, the effects of neuraminidase inhibitors on viral release from primary cultures of human tracheal epithelial cells, which retain functions of the original tissues, have not been studied. The effects of neuraminidase inhibitors on the replication of the pandemic influenza virus [A/Sendai‐H/N0633/2009 (H1N1) pdm09] and the seasonal influenza virus [A/Sendai‐H/216/2009 (H1N1)] that was isolated during the 2008–2009 season were examined. The virus stocks were generated by infecting tracheal cells with the pandemic or seasonal influenza virus. Four types of inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) reduced pandemic viral titers and concentrations of the cytokines interleukin‐6 and tumor necrosis factor‐α in supernatants and viral RNA in cells. However, oseltamivir did not reduce seasonal viral titers, cytokine concentrations and viral RNA, and the 50% inhibitory concentration (IC50) of oseltamivir for neuraminidase activity in the seasonal virus was 300‐fold higher than that observed for the pandemic influenza virus. The seasonal influenza virus had an oseltamivir‐resistant genotype. The magnitude of the IC50 values of the neuraminidase inhibitors for the seasonal influenza virus was inversely related to the magnitude of the inhibitory effects on viral release. These methods for measuring the release of virus and inflammatory cytokines from primary cultures of human tracheal epithelium may provide useful information regarding the effects of neuraminidase inhibitors on influenza viruses. J. Med. Virol. 87: 25–34, 2015. © 2014 Wiley Periodicals, Inc.