Human Influenza Is More Effective than Avian Influenza at Antiviral Suppression in Airway Cells
Human Influenza Is More Effective than Avian Influenza at Antiviral Suppression in Airway Cells
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DOI：
10.1165/rcmb.2010-0157oc
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发表时间：
2011-06-01
影响因子：
6.4
通讯作者：
Wark, Peter A.
中科院分区：
文献类型：
--
作者：
Hsu, Alan Chen-Yu;Barr, Ian;Wark, Peter A.
气道上皮细胞是流感病毒感染的初始部位。气道上皮细胞对感染的先天免疫反应在限制病毒复制和传播中起重要作用。然而，人们对这种先天抗病毒反应对感染的重要性知之甚少。禽流感病毒是未来大流行的潜在来源；因此，研究宿主抗病毒系统对不同流感病毒的有效性是至关重要的。我们使用人流感病毒（H3N2）和低致病性禽流感病毒（H11N9）来评估和比较Calu-3细胞的抗病毒反应。感染后，H3N2在Calu-3细胞中的复制效率高于H11N9。这不是由于唾液酸残基在Calu-3细胞上的差异表达，而是由于H3N2干扰了宿主的抗病毒反应。与H11N9相比，H3N2诱导的抗病毒信号传导延迟，I型和III型IFN诱导受损。将非结构蛋白（NS1）编码基因转染支气管上皮细胞（BECs），发现H3N2 NS1比H11N9 NS1具有更强的抗病毒抑制作用。虽然低致病性禽流感病毒能够感染BECs，但人流感病毒在BECs中的复制比禽流感病毒更有效，这是由于两种NS1蛋白抑制抗病毒反应的能力不同。这表明，颠覆人类抗病毒反应可能是流感病毒适应人类宿主并引起疾病的重要条件。
Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.