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Abstract：
As traditional approaches to the control of dengue and Zika are insufficient, significant efforts have been made to develop utilization of the endosymbiotic bacterium Wolbachia to reduce the ability of mosquitoes to transmit pathogens. Although Wolbachia is known to inhibit flaviviruses in mosquitoes, including dengue virus (DENV) and Zika virus (ZIKV), it remains unclear how the endosymbiont interferes with viral replication cycle. In this study, we have carried out viral binding assays to investigate the impact of the Wolbachia strain wAlbB on the attachment of DENV serotype 2 (DENV-2) and ZIKV to Aedes aegypti Aag-2 cells. RNA interference (RNAi) was used to silence a variety of putative mosquito receptors of DENV that were differentially regulated by wAlbB in Aag-2 cells, in order to identify host factors involved in the inhibition of viral binding. Our results showed that, in addition to suppression of viral replication, Wolbachia strongly inhibited binding of both DENV-2 and ZIKV to Aag-2 cells. Moreover, the expression of two putative mosquito DENV receptors - dystroglycan and tubulin - was downregulated by wAlbB, and their knock-down resulted in the inhibition of DENV-2 binding to Aag-2 cells. These results will aid in understanding the Wolbachia-DENV interactions in mosquito and the development of novel control strategies for mosquito-borne diseases.
摘要：
由于传统的登革热和寨卡控制方法不足，已经做出了巨大的努力来开发内共生细菌Wolbachia的利用以降低蚊子传播病原体的能力。尽管已知Wolbachia可以抑制蚊子中的黄病毒，包括登革热病毒（DENV）和寨卡病毒（ZIKV），目前尚不清楚内共生体如何干扰病毒复制周期.在这项研究中,我们进行了病毒结合试验,以研究Wolbachia菌株wAlbB对DENV血清型2(DENV-2)和ZIKV附着于埃及伊蚊Aag-2细胞的影响.RNA干扰（RNAi）用于沉默Aag-2细胞中由wAlbB差异调节的DENV的多种推定蚊子受体，以鉴定参与抑制病毒结合的宿主因子。我们的研究结果表明,除了抑制病毒复制，Wolbachia强烈抑制DENV-2和ZIKV与Aag-2细胞的结合。此外，wAlbB下调了两种推定的蚊子DENV受体-营养不良聚糖和微管蛋白的表达，它们的敲低导致DENV-2与Aag-2细胞结合的抑制。这些结果将有助于了解Wolbachia-DENV在蚊子中的相互作用以及开发针对蚊子传播疾病的新型控制策略。
