Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis
Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis
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DOI：
10.1128/jvi.79.12.7819-7826.2005
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Peiris, JSM
中科院分区：
文献类型：
--
作者：
Cheung, CY;Poon, LLM;Peiris, JSM
严重急性呼吸综合征（SARS）的发病机制尚不清楚。巨噬细胞是呼吸系统中的关键哨兵细胞，因此比较人类巨噬细胞对SARS冠状病毒（SARS-CoV）和其他呼吸道病毒感染的反应是相关的。原代人单核细胞源性巨噬细胞体外感染SARS冠状病毒。通过测量正链和负链RNA的水平、SARS-CoV核蛋白的免疫荧光检测以及感染性病毒的滴定来监测病毒复制。应用基因芯片和实时定量逆转录PCR技术比较了SARS冠状病毒、人冠状病毒229 E和甲型H1N1流感病毒感染的巨噬细胞的基因表达谱。用酶联免疫吸附试验测定分泌的细胞因子。SARS-CoV在巨噬细胞中启动病毒基因转录和蛋白质合成，但复制失败，不产生感染性病毒。与人冠状病毒229 E和甲型流感病毒的情况相反，在SARS-CoV感染的巨噬细胞中很少或没有诱导β干扰素（IFN-β）。此外，SARS-CoV诱导趋化因子的表达，如CXCL 10/IFN-γ诱导蛋白10和CCL 2/单核细胞趋化蛋白1。IFN-β是先天免疫的关键成分，其诱导能力较差，而病毒诱导趋化因子的能力可以解释SARS发病机制的某些方面。
The pathogenesis of severe acute respiratory syndrome (SARS) remains unclear. Macrophages are key sentinel cells in the respiratory system, and it is therefore relevant to compare the responses of human macrophages to infections with the SARS coronavirus (SARS-CoV) and other respiratory viruses. Primary human monocyte-derived macrophages were infected with SARS-CoV in vitro. Virus replication was monitored by measuring the levels of positive- and negative-strand RNA, by immunofluorescence detection of the SARS-CoV nucleoprotein, and by titration of the infectious virus. The gene expression profiles of macrophages infected with SARS-CoV, human coronavirus 229E, and influenza A (H1N1) virus were compared by using microarrays and real-time quantitative reverse transcriptase PCR. Secreted cytokines were measured with an enzyme-linked immunosorbent assay. SARS-CoV initiated viral gene transcription and protein synthesis in macrophages, but replication was abortive and no infectious virus was produced. In contrast to the case with human coronavirus 229E and influenza A virus, there was little or no induction of beta interferon (IFN-beta) in SARS-CoV-infected macrophages. Furthermore, SARS-CoV induced the expression of chemokines such as CXCL10/IFN-gamma-inducible protein 10 and CCL2/monocyte chemotactic protein 1. The poor induction of IFN-beta, a key component of innate immunity, and the ability of the virus to induce chemokines could explain aspects of the pathogenesis of SARS.