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

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先天免疫反应

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作者:Hin Chu, Jie Zhou, Bosco Ho-Yin Wong, Cun Li, Zhong-Shan Cheng, Xiang Lin, Vincent Kwok-Man Poon, Tianhao Sun, Candy Choi-Yi Lau, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Kwok-Hung Chan, Liwei Lu, Bo-Jian Zheng, Kwok-Yung Yuen

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.

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