Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation
Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation
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DOI：
10.3390/v12060589
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发表时间：
2020-06-01
期刊：
影响因子：
4.7
通讯作者：
Wu, Nai-Huei
中科院分区：
文献类型：
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作者：
Shin, Dai-Lun;Yang, Wei;Wu, Nai-Huei
猪在甲型流感病毒（IAV）的种间传播中起着重要作用。猪气道上皮含有猪/人IAV（α 2，6-连接的唾液酸）和禽IAV（α 2，3-连接的唾液酸）的结合位点，因此如“混合容器理论”所建议的，适合于来自其他物种的病毒的适应。在这里，我们应用分化良好的猪气道上皮细胞来确定禽IAV的有效感染是否需要预先适应。此外，我们分析了唾液酸结合活性和病毒诱导的有害作用的影响。令人惊讶的是，在欧洲家禽和水禽中传播的禽IAV H1N1毒株显示出增加和延长的病毒复制，而不诱导强烈的先天免疫应答。在我们的精确切肺切片模型中，该病毒可以感染下呼吸道。用poly（I：C）和/或JAK/STAT途径抑制剂预处理细胞揭示干扰素刺激的先天免疫应答影响禽IAV在猪气道上皮中的复制，但不影响猪IAV的复制。进一步的研究表明，在IAV感染中，唾液酸的结合亲和力不是影响病毒对猪或人气道上皮细胞感染性的唯一因素，而在分化良好的雪貂气管上皮细胞中可能是至关重要的。综上所述，我们的研究结果表明，猪的作用是种间传播的船只应重新考虑，禽流感病毒感染哺乳动物的潜力需要更详细的特点。
Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (alpha 2,6-linked sialic acids) and avian IAV (alpha 2,3-linked sialic acids) and therefore is suited for adaptation of viruses from other species as suggested by the "mixing vessel theory". Here, we applied well-differentiated swine airway epithelial cells to find out whether efficient infection by avian IAV requires prior adaption. Furthermore, we analyzed the influence of the sialic acid-binding activity and the virus-induced detrimental effects. Surprisingly, an avian IAV H1N1 strain circulating in European poultry and waterfowl shows increased and prolonged viral replication without inducing a strong innate immune response. This virus could infect the lower respiratory tract in our precision cut-lung slice model. Pretreating the cells with poly (I:C) and/or JAK/STAT pathway inhibitors revealed that the interferon-stimulated innate immune response influences the replication of avian IAV in swine airway epitheliums but not that of swine IAV. Further studies indicated that in the infection by IAVs, the binding affinity of sialic acid is not the sole factor affecting the virus infectivity for swine or human airway epithelial cells, whereas it may be crucial in well-differentiated ferret tracheal epithelial cells. Taken together, our results suggest that the role of pigs being the vessel of interspecies transmission should be reconsidered, and the potential of avian H1N1 viruses to infect mammals needs to be characterized in more detail.