- 學位論文
探討埃及斑蚊唾液蛋白對登革病毒感染力之影響
Effects of mosquito saliva proteins on dengue virus infectivity in Aedes aegypti
摘要
蚊子是許多疾病的傳播媒介，例如：瘧疾、登革熱、西尼羅熱、屈躬病、黃熱病以及茲卡等。當中，登革熱為熱帶地區重要的疾病之一。台灣在2014 至 2015 年間爆發嚴重的登革熱疫情，這兩年造成超過5 萬例的登革熱感染案例。然而目前卻無有效的疫苗及藥物上市。因此，如何預防病媒蚊的叮咬以及控制病媒蚊的數量為當前防治病蚊媒傳染疾病最重要的研究課題。登革熱的傳播主要是透過病媒蚊的叮咬。在叮咬的過程中，病媒蚊之唾液蛋白會隨著登革病毒一併進入到人體內。先前在哺乳類的研究中指出，蚊子唾腺中的蛋白會影響登革病毒的感染，但確切的機制為何目前尚不甚清楚。值得注意的是，並非所有唾腺中的蛋白會隨著唾液排出。因此，本研究以埃及斑蚊為研究模式，著重在探討蚊子分泌出的唾液蛋白在登革病毒感染宿主時所扮演的角色為何。我們的實驗結果顯示，登革病毒的 prM 蛋白會透過其蛋白上的醣和唾液蛋白進行交互作用，且唾液蛋白在登革病毒感染的過程中扮演相當重要的角色。更進一步，我們找出 calreticulin (CRT) 此唾液蛋白，發現其會和登革病毒 prM 蛋白進行結合。且此蛋白除了出現在唾液外，在埃及斑蚊的其他組織中也有表現，同時我們也證實 CRT 是調控登革病毒在埃及斑蚊體內複製的重要蛋白。再者，我們也發現當唾液中少了 CRT 此蛋白後，登革病毒之感染力明顯下降。本研究證實CRT 為登革病毒傳播及感染宿主時之重要唾液蛋白。透過了解唾液蛋白在登革病毒傳播時所扮演的角色，將提供未來規劃可行的方法以控制登革病毒的傳播。
並列摘要
Mosquitoes are one of the fatal animals in the world and they act as vectors for several diseases, including malaria, dengue fever, West Nile fever, chikungunya and Zika. Among these diseases, dengue fever is currently one of the world’s most important tropical diseases. More than 50 thousand cases were reported in 2014 and 2015 in Taiwan. However, there is no effective dengue vaccine or drug available so far. Hence, vector control becomes an alternative strategy for dengue control. Dengue virus (DENV) is transmitted to humans by the mosquito Aedes aegypti during the blood meal. In the meantime, DENV and saliva proteins are inoculated into human skin. Previous studies have indicated that proteins from mosquito salivary gland may influence the DENV infectivity in the mammalian host. However, the exact mechanisms of saliva-mediated infectivity enhancement remain unknown largely. It is worth noting that not all the proteins in the salivary gland were secreted. Therefore, the aim of this study is to investigate the role of mosquito saliva on dengue virus infectivity in Aedes aegypti. Our results showed that mosquito saliva proteins are associated with dengue virus proteins in Aedes aegypti via glycan-protein interactions, and these interactions are crucial for dengue virus infectivity. Furthermore, we identified a saliva protein named calreticulin (CRT) to be interacted with dengue prM protein in the mosquito saliva. We found that CRT not only expressed in mosquito saliva but also other tissues. We also demonstrated that CRT is essential for DENV replication in Aedes aegypti. Furthurmore, silencing of CRT resulted in significant reduction of dengue virus infectivity in the mosquito saliva, indicating that CRT plays an important role in DENV transmission. Understanding the role of saliva proteins in DENV transmission will provide novel approaches for the development of new tools for the control of arbovirus-borne diseases transmitted by the same vector.
參考文獻
延伸閱讀
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