伊蚊C型凝集素mosGCTL-2是登革病毒感染相关的重要蛋白质
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1.1)北京大学深圳研究生院,深圳 518055;2.2)南方科技大学生物系,深圳 518055;3.3)武汉大学高等研究院,武汉 430072;4.4)深圳湾实验室,深圳 518055;5.5)深圳市龙华区疾病预防控制中心,深圳 518109

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国家重点研发计划(2018YFA0507103),国家自然科学基金(31870719),深圳市科创委基础研究项目(JCYC20160331-115853521,JCYJ20170307-110657570,JCYJ20170817110434640),深圳市三名工程项目(SZSM201809085),中国博士后科学基金(2018M641077)和科技部重大研发专项(2018ZX09711003-003-004)资助项目.


C-type Lectin Protein mosGCTL-2 From Aedes aegypti is a Novel Factor for Dengue Virus Infection
Author:
Affiliation:

1.1)School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China;2.2)Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China;3.3)Institute for Advanced Studies, Wuhan University, Wuhan 430072, China;4.4)Shenzhen Bay Laboratory, Shenzhen 518055, China;5.5)Joint Laboratory for Infectious Disease Prevention and Control, Hygienic Section of Longhua Center for Disease Control and Prevention, Longhua District, Shenzhen 518109, China

Fund Project:

This work was supported by grants from the National Key R&D Program of China (2018YFA0507103), The National Natural Science Foundation of China (31870719), Shenzhen STIC (JCYC20160331-115853521), and Shenzhen San-Ming Project (SZSM201809085), Shenzhen STIC (JCYJ20170307-110657570), Chinese Postdoctoral Science Foundation Project (2018M641077), Ministry of Science and Technology of China (2018ZX09711003-003-004), and Shenzhen STIC (JCYJ20170817110434640).

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    摘要:

    C型凝集素是一类含有糖结合结构域的蛋白质,从节肢动物到哺乳动物的C型凝集素都具有共同的基序,它在进化上相当保守,在免疫反应中发挥重要作用. 埃及伊蚊表达30多种C型凝集素蛋白,它是登革病毒的关键传播媒介,这些蛋白质对病毒和细菌感染均有至关重要的作用. 最近研究表明,C型凝集素mosGCTL-3与二型登革热病毒包膜蛋白具有相互作用,能够增强登革病毒对埃及伊蚊的感染. 在本文中,我们发现了C型凝集素蛋白mosGCTL-2具有与mosGCTL-3类似的功能. 两种C型凝集素mosGCTL-2和mosGCTL-3的氨基酸残基序列一致性高达43.56%. 为研究mosGCTL-2在登革病毒蚊媒传播中的作用,我们通过果蝇S2细胞表达系统表达纯化了mosGCTL-2蛋白. 结果表明,mosGCTL-2与二型登革热病毒包膜蛋白的结合具有钙离子依赖性. 进一步的研究表明,埃及伊蚊感染登革病毒能够诱导mosGCTL2表达上调,是二型登革热病毒感染埃及伊蚊所必需的蛋白质. 以上研究说明,mosGCTL-2蛋白可能是在登革热病毒感染埃及伊蚊中起重要作用的一种模式识别受体.

    Abstract:

    C-type lectins (CTLs) are a family of carbohydrate-binding proteins that share a common structural motif; they are quite conserved evolutionarily from arthropods to mammals and play an essential role in immune responses. Aedes aegypti is a pivotal vector for the dengue virus and expresses more than 30 types of C-type lectins, which are critical for both viral and bacterial infections. A recent study indicates that mosGCTL-3 interacts with a dengue virus-2 envelope protein (DENV-2 E protein) in vivo and in vitro thereby enhancing the infection of A. aegypti. Here, in this report we found another C-type lectin protein, mosGCTL-2 with important functions similar to mosGCTL-3. Results from the phylogenetic tree analysis suggested that there is sequence similarity between mosGCTL-2 and mosGCTL-3, with 43.56% of their amino acid sequences being identical. We constructed Drosophila S2 cell expression system to purify mosGCTL-2. In vitro experiments showed that mosGCTL-2 binds to the DENV-2 E protein through a calcium-dependent manner. The upregulation of mosGCTL-2 was noted in A. aegypti and was important for dengue virus 2 (DENV-2) infection in vivo. These findings suggest that mosGCTL-2 may be a pattern recognition receptor that performs an important function in the infection of A. aegypti by the dengue virus.

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吴宇杰,刘珊,张溪,李东阳,邬玉兰,孙京川,许少坚,任燕,汪涛,刘丽,宫君原.伊蚊C型凝集素mosGCTL-2是登革病毒感染相关的重要蛋白质[J].生物化学与生物物理进展,2019,46(12):1187-1196

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历史
  • 收稿日期:2019-09-19
  • 最后修改日期:2019-11-11
  • 接受日期:2019-11-14
  • 在线发布日期: 2020-04-23
  • 出版日期: 2019-12-20