Law Helen K W, Cheung Chung Yan, Ng Hoi Yee, Sia Sin Fun, Chan Yuk On, Luk Winsie, Nicholls John M, Peiris J S Malik, Lau Yu Lung
Department of Paediatrics and Adolescent Medicine, Hong Kong Jockey Club Clinical Research Centre, Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Blood. 2005 Oct 1;106(7):2366-74. doi: 10.1182/blood-2004-10-4166. Epub 2005 Apr 28.
Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV-infected DCs. The SARS-CoV-infected DCs showed low expression of antiviral cytokines (interferon alpha [IFN-alpha], IFN-beta, IFN-gamma, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1alpha [MIP-1alpha], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV.
严重急性呼吸综合征（SARS）发病头10天出现的淋巴细胞减少及病毒载量增加提示SARS冠状病毒（SARS-CoV）存在免疫逃逸。在本研究中，我们聚焦于在连接固有免疫和适应性免疫过程中发挥重要作用的树突状细胞（DC）。通过电子显微镜和免疫荧光观察发现，SARS-CoV可感染未成熟和成熟的人单核细胞衍生DC。DC中检测到SARS-CoV RNA负链提示病毒复制。然而，未观察到病毒RNA增加。采用细胞病变分析，在感染的DC及细胞培养上清液中未检测到病毒滴度增加，证实病毒复制不完全。在SARS-CoV感染的DC中未检测到凋亡或成熟的诱导。SARS-CoV感染的DC显示抗病毒细胞因子（干扰素α[IFN-α]、IFN-β、IFN-γ和白细胞介素12p40[IL-12p40]）表达较低，促炎细胞因子（肿瘤坏死因子α[TNF-α]和IL-6）中度上调，但炎症趋化因子（巨噬细胞炎性蛋白1α[MIP-1α]、正常T细胞激活后表达和分泌的调节因子[RANTES]）、10 kDa干扰素诱导蛋白[IP-10]和单核细胞趋化蛋白1[MCP-1]）显著上调。在趋化因子强烈上调背景下缺乏抗病毒细胞因子反应可能代表SARS-CoV的一种免疫逃逸机制。
