埃及斑蚊感染登革病毒對其生殖調控之影響

蚊子在許多傳染疾病當中扮演著相當重要的角色，主要是瘧疾、登革熱、黃熱病、西尼羅熱、絲蟲病等疾病傳播的媒介。其中，登革熱是一種不可輕忽而且具有威脅性的傳染病，根據世界衛生組織的統計，全世界至少有二十五億的人口是暴露在感染登革熱的風險當中，並且估計全球每年大約有5000萬個登革熱病例；而臺灣在2013年就有將近1000個登革熱病例。由於至今尚未有登革疫苗問世，再加上仍無有效對抗登革熱的藥物，所以目前為止對於登革熱只能採取支持性的療法；因此，藉由控制病媒蚊的數量來抑制蟲媒疾病傳播，並且發展新的病媒控制方法來防治登革熱，是現今重要的研究主題。本研究以埃及斑蚊做為研究模式，來探討病媒蚊在感染登革病毒時，其免疫系統與生殖調控之相關機制，希望藉由釐清其詳細調控機制，找出控制登革病毒傳播的可能性。從初步的實驗結果當中，我們發現埃及斑蚊感染登革病毒之後，埃及斑蚊之母蚊產卵數量有顯著下降的趨勢。為了深入瞭解埃及斑蚊感染登革病毒後對生殖調控的影響與其相關機制，我們首先想釐清登革病毒感染與埃及斑蚊卵黃生成的關係。初步結果發現當埃及斑蚊受到登革病毒感染之後，Vitellogenin (Vg) 的表現量無論是在轉錄還是轉譯的階段皆明顯被抑制；此外，我們更進一步發現母蚊之脂肪體中TOR訊息傳遞路徑下游之S6K磷酸化反應受到抑制。因此，我們認為登革病毒極有可能藉由影響TOR訊息傳遞路徑，以達到抑制埃及斑蚊產卵能力的效果。本研究結果將有助於未來應用在病媒傳病能力之研究及病媒控制策略之制訂。

關鍵字

埃及斑蚊；登革病毒； TOR 訊息傳遞路徑；卵黃生成作用；生殖

並列摘要

The female mosquito Aedes aegypti plays a pivotal role in bloodmeal acquisition and reproduction, and thereby dengue virus (DENV) transmission. Dengue fever is one of the most devastating arthropod-borne diseases. The WHO reported some 2.5 billion people were at risk from dengue and estimated that there may be 50 million cases of dengue infection worldwide every year. Almost 1000 cases of dengue infection were reported in Taiwan at 2013. Up to now, no effective dengue vaccine or drug has been developed. Therefore, any possible avenue for developing novel control strategies against mosquito-borne diseases is urgently needed. In our preliminary results, we showed a significant reduction of the egg production was exhibited in the mosquitoes infected with dengue virus. To elucidate the impact and underlying mechanisms of DENV infection on mosquito reproduction, we first examined the effects of vitellogenesis upon DENV infection. The expression of vitellogenin was significantly inhibited in terms of transcription and translation level when female mosquitoes were fed by infectious blood meal. Components of a nutrient-sensitive signaling pathway, the TOR signaling pathway, were examined in the dengue virus infected mosquitoes. We showed a significant inhibition of the phosphorylation of S6K, a downstream target of TOR signaling, in the mosquito fat body when taking an infectious blood meal. Our results indicated that DENV infection in the mosquito leads to the inhibition of egg production. This particular effect is regulated by TOR signaling pathway. Information gathered in this study will pave the way toward the establishment of efficient strategies for vector control by using molecular engineering approaches.

並列關鍵字

Aedes aegypti ； dengue virus ； TOR signaling ； vitellogenesis ； reproduction

參考文獻

Attardo, G. M., Hansen, I. A., & Raikhel, A. S. (2005). Nutritional regulation of vitellogenesis in mosquitoes: implications for anautogeny. Insect Biochem Mol Biol, 35(7), 661-675. doi: 10.1016/j.ibmb.2005.02.013

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Bhatt, S., Gething, P. W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L., . . . Hay, S. I. (2013). The global distribution and burden of dengue. Nature, 496(7446), 504-507. doi: 10.1038/nature12060

Carvalho, D. O., Costa-da-Silva, A. L., Lees, R. S., & Capurro, M. L. (2014). Two step male release strategy using transgenic mosquito lines to control transmission of vector-borne diseases. Acta Trop, 132 Suppl, S170-177. doi: 10.1016/j.actatropica.2013.09.023

Cowman, A. F., Berry, D., & Baum, J. (2012). The cellular and molecular basis for malaria parasite invasion of the human red blood cell. J Cell Biol, 198(6), 961-971. doi: 10.1083/jcb.201206112

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埃及斑蚊感染登革病毒對其生殖調控之影響

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