埃及斑蚊生殖調控路徑及宿主因子調控登革病毒之複製

Pathways of reproduction control and host factors regulating dengue virus replication in the mosquito Aedes aegypti

翁仕哲(Shih-Che Weng)

指導教授 ： 蕭信宏

國立臺灣大學/醫學院/微生物學研究所/博士(2020年)

https://doi.org/10.6342/NTU202000529

摘要

病媒蚊的生活史需要藉由吸取脊椎動物的血以完成其卵巢的發育。目前已知有某些病媒蚊能傳播人類重要疾病的病原體。因而，了解如何調節病媒蚊生殖調控與病原體複製的機制，對於開發嶄新的蚊媒蚊控制策略是重要的。Wnt訊息傳遞和未折疊的蛋白反應（UPR）在果蠅的胚胎發育和細胞的逆境反應中扮演重要的角色。但是，我們對於這兩種途徑與病媒蚊中卵黃生成的交互作用了解甚少。此外，先前在哺乳類細胞的研究中也發現，登革病毒感染需要高血糖和蛋白質的轉錄後修飾（例如: SUMOylation），這些對哺乳動物中的病毒複製是重要的。然而，對於登革病毒的主要傳播媒介埃及斑蚊中，吸血時血液中葡萄糖濃度和病媒蚊體內蛋白質SUMOylation對登革熱病毒複製的影響知之甚少。在本論文中，我們證明了Wnt和TOR信號之間的交互作用與埃及斑蚊生殖調控有關。我們也發現，在埃及斑蚊中，母蚊吸血後可以藉由活化未折疊的蛋白反應來啟動細胞自噬，而這些反應對於病媒蚊的生殖調控也扮演了重要的角色。另外，我們也證實了血糖和蛋白質SUMOylation有利於病毒在埃及斑蚊體內複製。

關鍵字

埃及斑蚊 ； 卵黃生成作用 ； Wnt 訊息傳遞路徑 ； 未折疊蛋白質反應 ； 細胞自噬 ； 登革病毒 ； 血醣 ； 蛋白質泛素化修飾

並列摘要

Vertebrate blood is required for mosquito egg development. Some mosquito species are known to act as vectors for pathogens that cause devastating diseases in humans. Hence, understanding the mechanisms regulating egg developmental and pathogens replication are important basis for developing novel approaches to combat mosquito-borne diseases. The Wnt signaling pathway and the unfolded protein response (UPR) are key events in embryonic development and cellular stress response in model organisms, such as Drosophila. However, the interactions between these two pathways and vitellogenesis are poorly understood in the mosquito. Moreover, the blood glucose and post-translational protein modification such as SUMOylation have been shown to be required for dengue virus infection and important for viral replication in mammals. However, little is known about the effect of glucose levels and protein SUMOylation on dengue virus replication in the mosquito. Here, I demonstrated that there is a crosstalk between Wnt and TOR signaling, which are involved in the regulation of mosquito reproduction. I also showed that the autophagy-mediated egg production in the mosquito A. aegypti is regulated by UPR. In addition, I demonstrated that blood glucose and protein SUMOylation are beneficial to the virus replication and facilitates the virus transmission in the mosquito via the AKT and TOR signaling.

並列關鍵字

Aedes aegypti ； vitellogenesis ； Wnt signaling pathway ； unfolded protein response, UPR ； autophagy ； dengue virus ； blood glucose ； protein SUMOylation

參考文獻

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