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中东呼吸综合征冠状病毒在单核细胞衍生的树突状细胞中的有效复制调节固有免疫反应。

Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response.

机构信息

Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, China; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, China; Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, China.

出版信息

Virology. 2014 Apr;454-455:197-205. doi: 10.1016/j.virol.2014.02.018. Epub 2014 Mar 7.

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) closely resembled severe acute respiratory syndrome coronavirus (SARS-CoV) in disease manifestation as rapidly progressive acute pneumonia with multi-organ dysfunction. Using monocyte-derived-dendritic cells (Mo-DCs), we discovered fundamental discrepancies in the outcome of MERS-CoV- and SARS-CoV-infection. First, MERS-CoV productively infected Mo-DCs while SARS-CoV-infection was abortive. Second, MERS-CoV induced significantly higher levels of IFN-γ, IP-10, IL-12, and RANTES expression than SARS-CoV. Third, MERS-CoV-infection induced higher surface expression of MHC class II (HLA-DR) and the co-stimulatory molecule CD86 than SARS-CoV-infection. Overall, our data suggests that the dendritic cell can serve as an important target of viral replication and a vehicle for dissemination. MERS-CoV-infection in DCs results in the production of a rich combination of cytokines and chemokines, and modulates innate immune response differently from that of SARS-CoV-infection. Our findings may help to explain the apparent discrepancy in the pathogenicity between MERS-CoV and SARS-CoV.

摘要

中东呼吸综合征冠状病毒(MERS-CoV)在疾病表现上与严重急性呼吸综合征冠状病毒(SARS-CoV)非常相似,表现为迅速进展的急性肺炎伴多器官功能障碍。我们使用单核细胞衍生的树突状细胞(Mo-DC)发现了 MERS-CoV 和 SARS-CoV 感染结果的根本差异。首先,MERS-CoV 可有效感染 Mo-DC,而 SARS-CoV 感染则失败。其次,MERS-CoV 诱导的 IFN-γ、IP-10、IL-12 和 RANTES 表达水平明显高于 SARS-CoV。第三,MERS-CoV 感染诱导的 MHC Ⅱ类(HLA-DR)和共刺激分子 CD86 的表面表达水平高于 SARS-CoV 感染。总的来说,我们的数据表明树突状细胞可作为病毒复制的重要靶标和传播载体。MERS-CoV 感染 DC 会产生丰富的细胞因子和趋化因子组合,并以不同于 SARS-CoV 感染的方式调节先天免疫反应。我们的发现可能有助于解释 MERS-CoV 和 SARS-CoV 之间明显不同的致病性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd26/7111975/9e9745ddb709/gr1_lrg.jpg

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