登革出血热由感染了登革病毒的蚊子的叮咬传播，每年感染5000多万人，造成大约2万人死亡，但目前还没有针对该病毒的疫苗或疗法。对被该病毒作为目标的宿主蛋白以及负责控制炎症反应及抗病毒免疫的信号通道的识别，是制定治疗方法所必需的。Szu-Ting  Chen等人发现，登革病毒能与C-型凝集素CLEC45A发生相互作用，因而朝着这个目标迈进了一步。这种相互作用能够促进“促炎细胞因子”（pro-inflammatory  cytokines）的生成，在一个小鼠模型中有助于致命疾病的形成。

英文原文：

Nature 453, 672-676 (29 May 2008) | doiminmax_bound="true">:10.1038/nature07013; Received 29 February 2008; Accepted 18 April 2008; Published online 21 May 2008

CLEC5A is critical for dengue-virus-induced lethal disease

Szu-Ting Chen1, Yi-Ling Lin2,3, Ming-Ting Huang1, Ming-Fang Wu1, Shih-Chin Cheng1, Huan-Yao Lei4, Chien-Kuo Lee5, Tzyy-Wen Chiou6, Chi-Huey Wong3 & Shie-Liang Hsieh1,3,7

Department and Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan

Institute of Biomedical Sciences, and,

Genomics Research Center, Academia Sinica, Taipei 115, Taiwan

Department of Microbiology and Immunology, National Cheng Kung University, Tainan 701, Taiwan

Institute of Immunology, National Taiwan University, Taipei 100, Taiwan

Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan

Immunology Research Center, National Yang-Ming University & Taipei Veterans General Hospital, Taipei 112, Taiwan

Correspondence to: Shie-Liang Hsieh1,3,7 Correspondence and requests for materials should be addressed to S-L H. (Email: slhsieh@ym.edu.tw or Email: slhsieh@gate.sinica.edu.tw).

Dengue haemorrhagic fever and dengue shock syndrome, the most severe responses to dengue virus (DV) infection, are characterized by plasma leakage (due to increased vascular permeability) and low platelet counts1, 2. CLEC5A (C-type lectin domain family 5, member A; also known as myeloid DAP12-associating lectin (MDL-1))3 contains a C-type lectin-like fold similar to the natural-killer T-cell C-type lectin domains and associates with a 12-kDa DNAX-activating protein (DAP12)4 on myeloid cells. Here we show that CLEC5A interacts with the dengue virion directly and thereby brings about DAP12 phosphorylation. The CLEC5A–DV interaction does not result in viral entry but stimulates the release of proinflammatory cytokines. Blockade of CLEC5A–DV interaction suppresses the secretion of proinflammatory cytokines without affecting the release of interferon-, supporting the notion that CLEC5A acts as a signalling receptor for proinflammatory cytokine release. Moreover, anti-CLEC5A monoclonal antibodies inhibit DV-induced plasma leakage, as well as subcutaneous and vital-organ haemorrhaging, and reduce the mortality of DV infection by about 50% in STAT1-deficient mice. Our observation that blockade of CLEC5A-mediated signalling attenuates the production of proinflammatory cytokines by macrophages infected with DV (either alone or complexed with an enhancing antibody) offers a promising strategy for alleviating tissue damage and increasing the survival of patients suffering from dengue haemorrhagic fever and dengue shock syndrome, and possibly even other virus-induced inflammatory diseases.