Aedes albopictus D7 Salivary Protein Prevents Host Hemostasis and Inflammation.

Aedes albopictus D7 Salivary Protein Prevents Host Hemostasis and Inflammation.
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DOI:
10.3390/biom10101372
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发表时间:
2020-09-27
期刊:
影响因子:
5.5
通讯作者:
Calvo E
Calvo E
中科院分区:
生物学2区
文献类型:
--
作者:
Martin-Martin I;Smith LB;Chagas AC;Sá-Nunes A;Shrivastava G;Valenzuela-Leon PC;Calvo E

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蚊子将唾液注入宿主皮肤,通过阻止止血的活性化合物促进血餐的获取。D 7蛋白是蚊子唾液中最丰富的组分之一,并作为生物胺和类花生酸的清除剂。D 7家族的几个成员已经在生化水平上进行了表征;然而,迄今为止还没有在白纹伊蚊中进行过研究,白纹伊蚊是几种虫媒病毒的允许载体,导致广泛的人类发病率和死亡率。在这里,我们报告的结合能力的D 7长型蛋白质从Ae。albopictus(AlboD 7 L1)的结构,并将其模型结构与先前求解的D 7结构进行了比较。通过离体血小板聚集和体内白细胞募集实验证明了AlboD 7 L1的生理功能。AlboD 7 L1结合宿主止血激动剂,包括生物胺、白三烯和血栓烷A2类似物U-46619。AlboD 7 L1蛋白模型预测通过其N-末端结构域结合生物脂质,而C-末端结构域结合生物胺。我们证明了AlboD 7 L1作为血小板聚集和中性粒细胞和嗜酸性粒细胞的细胞募集的抑制剂的生物学功能。总而言之,这项研究加强了D 7唾液蛋白作为抗止血和抗炎分子的生理相关性,这些分子有助于蚊子的血液喂养。
Mosquitoes inject saliva into the host skin to facilitate blood meal acquisition through active compounds that prevent hemostasis. D7 proteins are among the most abundant components of the mosquito saliva and act as scavengers of biogenic amines and eicosanoids. Several members of the D7 family have been characterized at the biochemical level; however, none have been studied thus far in Aedes albopictus, a permissive vector for several arboviruses that causes extensive human morbidity and mortality. Here, we report the binding capabilities of a D7 long form protein from Ae. albopictus (AlboD7L1) by isothermal titration calorimetry and compared its model structure with previously solved D7 structures. The physiological function of AlboD7L1 was demonstrated by ex vivo platelet aggregation and in vivo leukocyte recruitment experiments. AlboD7L1 binds host hemostasis agonists, including biogenic amines, leukotrienes, and the thromboxane A2 analog U-46619. AlboD7L1 protein model predicts binding of biolipids through its N-terminal domain, while the C-terminal domain binds biogenic amines. We demonstrated the biological function of AlboD7L1 as an inhibitor of both platelet aggregation and cell recruitment of neutrophils and eosinophils. Altogether, this study reinforces the physiological relevance of the D7 salivary proteins as anti-hemostatic and anti-inflammatory molecules that help blood feeding in mosquitoes.
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