| Summary: | 碩士 === 國立臺灣大學 === 微生物學研究所 === 107 === Mosquitoes act as vectors to carry and spread disease to humans, including malaria, chikungunya, West Nile fever, dengue fever, and Zika. Among these diseases, dengue fever is currently one of the world’s most important tropical diseases. According to the statistics from World Health Organization, 390 million individuals were infected each year, with up to 96 million symptomatic infections. Taiwan is also one of the prevalent areas of dengue fever, and a serious outbreak occurred in 2014 and 2015 with more than 50,000 cases. Although dengue vaccines have been developed recently, their effectiveness and safety remain to be further elucidated. Hence, vector control becomes an alternative strategy for dengue control. Signal peptidases, which have been shown to be required for flavivirus replication that convert secretory and some membrane proteins to their mature forms by cleaving their signal peptides. Absence of signal peptides resulted in reduced yield of Flaviviridae family members. In the dengue mosquito vector Aedes aegypti, several signal peptidases have been identified but their functions were largely unknown. To investigate the role of signal peptidases on dengue virus reproduction in Aedes aegypti, two signal peptidases gene, SPCS2 and SEC11, were silenced by reverse genetic approach. Silencing of SPCS2 and SEC11 resulted in significant reduction of dengue virus replication. Interestingly, we showed that two isoforms of dengue virus envelope protein were exhibited in the mosquito midgut, salivary gland and fat body whereas only one isoform of E protein was detected in the saliva. We speculate that two isoforms may be generated by an additional cleavage of E protein, and this cleavage is important for dengue virus replication or transmission. We therefore generated a point mutation on the predicted cleavage site of the E protein indicating that K36 may be the additional cleavage site of E protein. In the future, we will investigate the effects of signal peptidases in the cleavage of E protein.
|
|---|
