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Anopheles stephensi Dual Oxidase Silencing Activates the Thioester-Containing Protein 1 Pathway to Suppress Plasmodium Development.
Journal of Innate Immunity ( IF 5.3 ) Pub Date : 2019-03-29 , DOI: 10.1159/000497417
Parik Kakani 1 , Mithilesh Kajla 1, 2 , Tania Pal Choudhury 1 , Lalita Gupta 1, 3 , Sanjeev Kumar 4, 5
Affiliation  

We characterized the dual oxidase (Duox) gene in the major Indian malaria vector Anopheles stephensi, which regulates the generation of reactive oxygen species. The AsDuox gene encodes for a 1,475-amino-acid transmembrane protein that contains an N-terminal noncytoplasmic heme peroxidase domain, a calcium-binding domain, seven transmembrane domains, and a C-terminal cytoplasmic NADPH domain. Phylogenetic analyses revealed that A. stephensi Duox protein is highly conserved and shares 97-100% amino acid identity with other anopheline Duoxes. AsDuox is expressed in all the developmental stages of A. stephensi and the pupal stages revealed relatively higher expressions. The Duox gene is induced in Plasmodium-infected mosquito midguts, and RNA interference-mediated silencing of this gene suppressed parasite development through activation of the thioester-containing protein 1 pathway. We propose that this highly conserved anopheline Duox, being a Plasmodium agonist, is an excellent target to control malaria parasite development inside the insect host.

中文翻译:

斯蒂芬按蚊双氧化酶沉默可激活含硫酯的蛋白1途径,以抑制疟原虫的发育。

我们在主要的印度疟疾载体按蚊Anopheles stephensi中表征了双氧化酶(Duox)基因,该基因可调节活性氧的产生。AsDuox基因编码一个1,475个氨基酸的跨膜蛋白,其中包含一个N端非胞质血红素过氧化物酶结构域,一个钙结合结构域,七个跨膜结构域和一个C端胞质NADPH结构域。系统发育分析表明,A。stephensi Duox蛋白是高度保守的,与其他按蚊Duoxes具有97-100%的氨基酸同一性。AsDuox在A. stephensi的所有发育阶段都有表达,而stages阶段则表现出相对较高的表达。Duox基因是在疟原虫感染的蚊子中肠中诱导产生的,RNA干扰介导的该基因沉默通过激活含硫酯的蛋白1途径抑制了寄生虫的发育。我们认为这种高度保守的按蚊Duox是疟原虫的激动剂,是控制昆虫寄主内部疟疾寄生虫发育的极佳靶标。
更新日期:2019-11-01
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