Shanmuganatham Karthik K, Jones Jeremy C, Marathe Bindumadhav M, Feeroz Mohammed M, Jones-Engel Lisa, Walker David, Turner Jasmine, Rabiul Alam S M, Kamrul Hasan M, Akhtar Sharmin, Seiler Patrick, McKenzie Pamela, Krauss Scott, Webby Richard J, Webster Robert G
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Department of Zoology, Jahangirnagar University, Dhaka 1342, Bangladesh.
Emerg Microbes Infect. 2016 Apr 20;5(4):e35. doi: 10.1038/emi.2016.29.
H9N2 avian influenza viruses are continuously monitored by the World Health Organization because they are endemic; they continually reassort with H5N1, H7N9 and H10N8 viruses; and they periodically cause human infections. We characterized H9N2 influenza viruses carrying internal genes from highly pathogenic H7N3 viruses, which were isolated from chickens or quail from live-bird markets in Bangladesh between 2010 and 2013. All of the H9N2 viruses used in this study carried mammalian host-specific mutations. We studied their replication kinetics in normal human bronchoepithelial cells and swine tracheal and lung explants, which exhibit many features of the mammalian airway epithelium and serve as a mammalian host model. All H9N2 viruses replicated to moderate-to-high titers in the normal human bronchoepithelial cells and swine lung explants, but replication was limited in the swine tracheal explants. In Balb/c mice, the H9N2 viruses were nonlethal, replicated to moderately high titers and the infection was confined to the lungs. In the ferret model of human influenza infection and transmission, H9N2 viruses possessing the Q226L substitution in hemagglutinin replicated well without clinical signs and spread via direct contact but not by aerosol. None of the H9N2 viruses tested were resistant to the neuraminidase inhibitors. Our study shows that the Bangladeshi H9N2 viruses have the potential to infect humans and highlights the importance of monitoring and characterizing this influenza subtype to better understand the potential risk these viruses pose to humans.
H9N2禽流感病毒一直受到世界卫生组织的持续监测，因为它们呈地方性流行；它们不断与H5N1、H7N9和H10N8病毒进行重配；并且它们会定期导致人类感染。我们对携带高致病性H7N3病毒内部基因的H9N2流感病毒进行了特征分析，这些病毒于2010年至2013年间从孟加拉国活禽市场的鸡或鹌鹑中分离得到。本研究中使用的所有H9N2病毒都带有哺乳动物宿主特异性突变。我们研究了它们在正常人支气管上皮细胞以及猪气管和肺外植体中的复制动力学，这些细胞和组织展现出许多哺乳动物气道上皮的特征，并可作为哺乳动物宿主模型。所有H9N2病毒在正常人支气管上皮细胞和猪肺外植体中都能复制到中高滴度，但在猪气管外植体中的复制受到限制。在Balb/c小鼠中，H9N2病毒无致死性，能复制到中等偏高滴度，且感染局限于肺部。在人类流感感染和传播的雪貂模型中，血凝素中具有Q226L替代的H9N2病毒复制良好，无临床症状，可通过直接接触传播，但不能通过气溶胶传播。所测试的H9N2病毒均对神经氨酸酶抑制剂不耐药。我们的研究表明，孟加拉国的H9N2病毒具有感染人类的潜力，并强调了监测和鉴定这种流感亚型以更好地了解这些病毒对人类构成的潜在风险的重要性。
