Role of Itk signalling in the interaction between influenza A virus and T-cells
Role of Itk signalling in the interaction between influenza A virus and T-cells
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DOI：
10.1099/vir.0.041228-0
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发表时间：
2012-05-01
影响因子：
3.8
通讯作者：
Chen, Ji-Long
中科院分区：
文献类型：
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作者：
Fan, Kewei;Jia, Yinping;Chen, Ji-Long
尽管 T 细胞介导的流感病毒免疫反应已被广泛研究，但关于流感病毒与 T 细胞之间与人类和动物严重疾病相关的直接相互作用的信息却很少。为了解决这些问题，我们利用BALB/c小鼠模型结合感染A/WSN/33流感病毒的原代T细胞来研究流感病毒在体内是否对T细胞具有亲和力。我们观察到感染小鼠的脾脏和胸腺中有一小部分CD4+T细胞和CD8+T细胞表达病毒蛋白。很大一部分小鼠原代T细胞表现出α-2,6唾液酸连接的流感病毒受体的表达，并直接被甲型流感病毒感染。这些实验表明，存在一群易受甲型流感病毒感染的 T 细胞。此外，我们利用人类 Jurkat T 细胞来研究病毒与 T 细胞的相互作用，特别强调了解 Itk（白细胞介素 2 诱导型 T 细胞激酶）（一种调节 T 细胞活化的 Tec 家族酪氨酸激酶）是否参与 T 细胞的病毒感染。有趣的是，流感病毒感染导致 Itk 向质膜的募集增加，磷脂酶 C-gamma 1 (PLC-gamma 1) 磷酸化水平增加，这表明 Itk/PLC-gamma 1 信号传导被病毒感染激活。我们证明，Itk 的缺失会抑制甲型流感病毒的复制，而 Itk 的过度表达会增加病毒的复制。这些结果表明，Itk 是流感病毒在受感染 T 细胞中有效复制所必需的。
Although the T-cell-mediated immune response to influenza virus has been studied extensively, little information is available on the direct interaction between influenza virus and T-cells that pertains to severe diseases in humans and animals. To address these issues, we utilized the BALB/c mouse model combined with primary T-cells infected with A/WSN/33 influenza virus to investigate whether influenza virus has an affinity for T-cells in vivo. We observed that small proportions of CD4(+) T-cells and CD8(+) T-cells in spleen and thymus expressed viral proteins in infected mice. A significant proportion of mouse primary T-cells displayed expression of alpha-2,6 sialic acid-linked influenza virus receptor and were infected directly by influenza A virus. These experiments reveal that there exists a population of T-cells that is susceptible to influenza A virus infection. Furthermore, we employed human Jurkat T-cells to investigate the virus-T-cell interaction, with particular emphasis on understanding whether Itk (interleukin-2-inducible T-cell kinase), a Tec family tyrosine kinase that regulates T-cell activation, is involved in virus infection of T-cells. Interestingly, influenza virus infection resulted in an increased recruitment of Itk to the plasma membrane and an increased level of phospholipase C-gamma 1 (PLC-gamma 1) phosphorylation, suggesting that Itk/PLC-gamma 1 signalling is activated by the virus infection. We demonstrated that depletion of Itk inhibited the replication of influenza A virus, whereas overexpression of Itk increased virus replication. These results indicate that Itk is required for efficient replication of influenza virus in infected T-cells.