Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.
Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.
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用于预防登革热的蚊子 C 型凝集素传播阻断抗体
DOI：
10.1371/journal.ppat.1003931
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发表时间：
2014-02
期刊：
影响因子：
6.7
通讯作者：
Cheng G
中科院分区：
文献类型：
--
作者：
Liu Y;Zhang F;Liu J;Xiao X;Zhang S;Qin C;Xiang Y;Wang P;Cheng G
C型凝集素是一类具有碳水化合物结合活性的蛋白质。哺乳动物或节肢动物中的几种C型凝集素被用作受体或附着因子以促进黄病毒入侵。我们先前在埃及伊蚊中鉴定了一种C型凝集素，命名为蚊子半乳糖特异性C型凝集素-1（mosGCTL-1），促进西尼罗河病毒（WNV）在细胞膜上的附着。在这里，我们首先确定了9 A。埃及伊蚊mosGCTL基因是促进DENV-2感染的关键易感因子，其中mosGCTL-3的作用最为显著。我们发现，在DENV-2感染的蚊子组织中，mosGCTL-3被诱导，并且该蛋白在体外和体内与DENV-2表面包膜（E）蛋白和病毒粒子相互作用。另外，其他mosGCTL与DENV-2 E蛋白相互作用，表明DENV可能利用多个mosGCTL作为配体来促进载体的感染。促进病原体入侵的媒介易感性因子可能被探索为破坏微生物从脊椎动物宿主获得的靶点。事实上，针对mosGCTL的抗血清的膜血喂养显著降低了蚊子的感染率。因此，针对mosGCTL的免疫是预防登革热感染的可行方法。我们的研究为开发阻断传播的疫苗提供了未来的途径，该疫苗可以中断登革热病毒的生命周期并减少疾病负担。
C-type lectins are a family of proteins with carbohydrate-binding activity. Several C-type lectins in mammals or arthropods are employed as receptors or attachment factors to facilitate flavivirus invasion. We previously identified a C-type lectin in Aedes aegypti, designated as mosquito galactose specific C-type lectin-1 (mosGCTL-1), facilitating the attachment of West Nile virus (WNV) on the cell membrane. Here, we first identified that 9 A. aegypti mosGCTL genes were key susceptibility factors facilitating DENV-2 infection, of which mosGCTL-3 exhibited the most significant effect. We found that mosGCTL-3 was induced in mosquito tissues with DENV-2 infection, and that the protein interacted with DENV-2 surface envelop (E) protein and virions in vitro and in vivo. In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. The vectorial susceptibility factors that facilitate pathogen invasion may potentially be explored as a target to disrupt the acquisition of microbes from the vertebrate host. Indeed, membrane blood feeding of antisera against mosGCTLs dramatically reduced mosquito infective ratio. Hence, the immunization against mosGCTLs is a feasible approach for preventing dengue infection. Our study provides a future avenue for developing a transmission-blocking vaccine that interrupts the life cycle of dengue virus and reduces disease burden.
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影响因子：
6.7
作者：
Gunn BM;Morrison TE;Whitmore AC;Blevins LK;Hueston L;Fraser RJ;Herrero LJ;Ramirez R;Smith PN;Mahalingam S;Heise MT
通讯作者：
Heise MT
影响因子：
3.7
作者：
Chowdhury DR;Angov E;Kariuki T;Kumar N
通讯作者：
Kumar N
影响因子：
64.5
作者：
Cheng G;Cox J;Wang P;Krishnan MN;Dai J;Qian F;Anderson JF;Fikrig E
通讯作者：
Fikrig E
影响因子：
5.4
作者：
Bai, Fengwei;Town, Terrence;Fikrig, Erol
通讯作者：
Fikrig, Erol
影响因子：
4.4
作者：
Baldwin, TA;Ostergaard, HL
通讯作者：
Ostergaard, HL