Identification of the extracellular metallo-endopeptidases ADAM and ADAMTS in the yellow fever mosquito Aedes aegypti.
Identification of the extracellular metallo-endopeptidases ADAM and ADAMTS in the yellow fever mosquito Aedes aegypti.
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黄热病蚊子埃及伊蚊细胞外金属内肽酶 ADAM 和 ADAMTS 的鉴定。
DOI：
10.1016/j.ibmb.2022.103815
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发表时间：
2022
影响因子：
3.8
通讯作者：
Franz,AlexanderWE
中科院分区：
文献类型：
--
作者：
Herd,ChristieS;Yu,Xiudao;Cui,Yingjun;Franz,AlexanderWE
埃及伊蚊是登革热、寨卡、黄热病和基孔肯雅（CHIKV）病毒的主要媒介，这些病毒在世界热带地区的人群中引起显著的发病率和死亡率。虫媒病毒从脊椎动物宿主体内摄取病毒血餐后，需要感染蚊子的中肠上皮细胞，然后通过穿过周围的基底层（BL）排出中肠，传播到次级组织并感染这些组织。一旦唾液腺被感染，病毒就随着蚊子在探测过程中释放的唾液沿着传播给脊椎动物宿主。由于血粉摄入引起的中肠组织扩张导致中肠结构重塑，并促进病毒从器官传播。以前，我们描述了Ae的基质金属蛋白酶（MMP）。埃及伊蚊的锌离子依赖性内肽酶（Metzincins），并显示MMP活性在中肠BL重排作为血粉摄入和随后消化的结果，从而影响虫媒病毒从中肠传播。埃及伊蚊，其形成Metzincin超家族内的另一个主要的多结构域蛋白酶组，并且在细胞外基质（ECM）重塑过程中具有活性。在Ae中鉴定出7种不同的ADAM和5种ADAMTS。埃及人。鉴定的蚊子ADAM的功能蛋白结构域结构类似于人ADAM 10、ADAM 12和ADAM 17的结构域结构，而5种蚊子ADAMTS中有2种具有人的直系同源物。Ae. aegyptiADAM/ADAMTS在未成熟的形式，整个身体女性，中肠，卵巢组织中的蛋白酶在变态，血粉摄取/消化，和女性生殖过程中表现出转录活性。针对ADAM 10a和ADAM 12 c的定制抗体显示，两者都在中肠和卵巢组织中强烈表达。此外，在感染后24 h，ADAM 12 c的瞬时沉默显著降低了CHIKV的胴体感染率，而在同一时间点，ADAM 12 a的沉默显著增加了次级组织中的病毒滴度。我们的研究结果表明，在这些选定的蚊子组织中的几个ADAM/ADAMTS的功能特异性。
The mosquitoAedes aegyptiis a major vector for dengue, Zika, yellow fever, and chikungunya (CHIKV) viruses, which cause significant morbidity and mortality among human populations in the tropical regions of the world. Following ingestion of a viremic bloodmeal from a vertebrate host, an arbovirus needs to productively infect the midgut epithelium of the mosquito.De novosynthesized virions then exit the midgut by traversing the surrounding basal lamina (BL) in order to disseminate to secondary tissues and infect those. Once the salivary glands are infected, the virus is transmitted to a vertebrate host along with saliva released during probing of the mosquito. Midgut tissue distention due to bloodmeal ingestion leads to remodeling of the midgut structure and facilitates virus dissemination from the organ. Previously, we described the matrix-metalloproteinases (MMP) ofAe. aegyptias zinc ion dependent endopeptidases (Metzincins) and showed MMP activity during midgut BL rearrangement as a consequence of bloodmeal ingestion and subsequent digestion thereby affecting arbovirus dissemination from the midgut.Here we investigate the ADAM/ADAMTS ofAe. aegypti, which form another major group of multi-domain proteinases within the Metzincin superfamily and are active during extra-cellular matrix (ECM) remodeling. Seven different ADAM and five ADAMTS were identified inAe. aegypti. The functional protein domain structures of the identified mosquito ADAM resembled those of human ADAM10, ADAM12, and ADAM17, while two of the five mosquito ADAMTS had human orthologs. Expression profiling ofAe. aegyptiADAM/ADAMTS in immature forms, whole body-females, midguts, and ovarian tissues showed transcriptional activity of the proteinases during metamorphosis, bloodmeal ingestion/digestion, and female reproduction. Custom-made antibodies to ADAM10a and ADAM12c showed that both were strongly expressed in midgut and ovarian tissues. Furthermore, transient silencing of ADAM12c significantly reduced the carcass infection rate with CHIKV at 24 h post-infection, while silencing of ADAM12a significantly increased viral titers in secondary tissues at the same time point. Our results indicate a functional specificity for several ADAM/ADAMTS in those selected mosquito tissues.