Diaz-Mitoma F, Alvarez-Maya I, Dabrowski A, Jaffey J, Frost R, Aucoin S, Kryworuchko M, Lapner M, Tadesse H, Giulivi A
Regional Virology Laboratory, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ony., Canada K1H 8L1.
J Clin Virol. 2004 Oct;31(2):100-12. doi: 10.1016/j.jcv.2004.04.006.
Influenza A virus is a major cause of morbidity and mortality worldwide. There is a large knowledge base on the immune response to influenza. However, few studies have focused on global gene expression in immune cells after antigenic challenge. A better understanding of the host immune response is required for the development of more efficient means of prevention and treatment of influenza. In this study, global gene expression in peripheral blood mononuclear cells (PBMCs) after influenza immunization was analyzed. The differential gene expression in antigen-stimulated and non-stimulated PBMCs was determined by cDNA microarrays. To determine whether a specific gene profile was present during a proliferative memory cell response to influenza antigens, gene expression in response to PHA was compared with antigen-stimulated PBMCs. PHA induced the upregulation of 201 genes while influenza virus antigen upregulated more than triple that is 630 genes out of 1700 genes analyzed. Both influenza antigen and PHA commonly upregulated 138 genes. Interferon (IFN)-related genes were induced by influenza but not by PHA. The interferon-gamma induced protein precursor 10 (IP-10) was upregulated 27-fold while the interferon-induced 54 kDa protein exhibited a 13-fold increase. The following gene families were also selectively upregulated by influenza antigens: complement ligands and receptors, T cell activation genes, growth factors, genes related to antigen processing and inflammatory responses. With PHA, the genes TNF-R, CTSG, CD3 delta, C8B, CRF1 and CCR2 had higher expression compared with the viral antigen stimulation. Neutrophil defensins alpha-1 and two C-C chemokines, proteins MIP-1-beta and MIP-4, were among the genes upregulated by both PHA and influenza antigens. The results suggest that interferon-induced genes are one of the main transcriptional targets during the immune response to influenza virus.
甲型流感病毒是全球发病和死亡的主要原因。关于流感免疫反应已有大量的知识基础。然而，很少有研究关注抗原刺激后免疫细胞中的全局基因表达。为了开发更有效的流感预防和治疗方法，需要更好地了解宿主免疫反应。在本研究中，分析了流感免疫后外周血单个核细胞（PBMC）中的全局基因表达。通过cDNA微阵列确定抗原刺激和未刺激的PBMC中的差异基因表达。为了确定在对流感抗原的增殖性记忆细胞反应过程中是否存在特定的基因谱，将对PHA反应的基因表达与抗原刺激的PBMC进行了比较。PHA诱导了201个基因的上调，而流感病毒抗原上调的基因超过其三倍，在分析的1700个基因中有630个基因上调。流感抗原和PHA共同上调了138个基因。干扰素（IFN）相关基因由流感诱导，但不由PHA诱导。干扰素-γ诱导蛋白前体10（IP-10）上调了27倍，而干扰素诱导的54 kDa蛋白增加了13倍。以下基因家族也被流感抗原选择性上调：补体配体和受体、T细胞活化基因、生长因子、与抗原加工和炎症反应相关的基因。与病毒抗原刺激相比，PHA刺激下TNF-R、CTSG、CD3δ、C8B、CRF1和CCR2基因有更高的表达。中性粒细胞防御素α-1以及两种C-C趋化因子，即MIP-1-β蛋白和MIP-4蛋白，是PHA和流感抗原均上调的基因。结果表明，干扰素诱导基因是流感病毒免疫反应过程中的主要转录靶点之一。
