DC-SIGN与mCEACAM1a分子相互作用调控鼠冠状病毒复制

树突细胞特异性细胞间黏附分子-3结合非整合素分子(dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin，DC-SIGN)和肝/淋巴结特异性细胞间黏附分子-3结合非整合素分子(liver/lymph node-specific intercellular adhesion molecules-3-grabbing non-integrin，L-SIGN)是钙离子依赖的C型凝集素受体，通过识别病毒粒子表面含甘露聚糖或果糖寡聚糖的分子介导病毒进入细胞，但其在调节病毒复制中的作用较少被关注。本研究通过建立稳定表达DC-SIGN和L-SIGN及其功能域嵌合体的细胞系，分析两者过表达对鼠冠状病毒复制的影响。结果显示，L-SIGN比DC-SIGN更能显著抑制病毒复制，这种差异与两者胞内区序列和基序组成不同有关；鼠冠状病毒感染导致细胞外信号调节激酶(extracellular signal-regulated kinase，ERK)信号通路分子磷酸化下调，过表达DC-SIGN和L-SIGN可抑制这种下调趋势。在没有鼠癌胚抗原相关细胞黏附分子1(mouse carcinoembryonic antigen-related cell adhesion molecule 1，mCEACAM1)存在时，DC-SIGN不能介导病毒感染。这些结果提示，DC-SIGN通过与mCEACAM1a分子相互作用和调节细胞信号通路分子功能以调控鼠冠状病毒复制。

Interaction of DC-SIGN and viral receptor mCEACAM1a regulates murine coronavirus replication

Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and liver/lymph node-specific intercellular adhesion molecules-3-grabbing non-integrin (L-SIGN) are calcium-dependent C-type lectin receptors (CLRs). Both proteins mediate the entrance of viruses by recognizing mannose or fructose oligosaccharides on the viral surface. However, potential regulation of DC-SIGN or L-SIGN on viral replication is neglected. In this study, we established murine cell lines stably expressing DC-SIGN, L-SIGN and their functional domain chimeras respectively, and analyzed the impacts of the expressed proteins on murine coronavirus replication. The results showed that L-SIGN had a more obviously inhibitory effect on viral replication than DC-SIGN, which was related to difference in the sequences. The inhibitory effect might act by antagonizing the downregulation of extracellular signal-regulated kinase (ERK) signaling pathway triggered by the virus. DC-SIGN was not found to directly mediate the entry of virus into receptor-unexpressed cell lines. The regulation of DC-SIGN and L-SIGN on the viral replication was dependent on the viral receptor mouse carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a) which might interact with DC-SIGN trimer on the cell surface. These results suggest that CLR can regulate the viral replication through interference with signaling events even if they cannot mediate directly the entry of the virus.