吸血蚋作为一种重要的虫媒传染病媒介，其抵抗虫媒病毒的机制尚不明确。我们发现云南特有蚋虫（版纳绳蚋）感染寨卡病毒后，宿主防御肽Siba3在唾液腺中上调表达最为显著；Siba3可有效抑制寨卡病毒在体内、体外的复制，可直接灭活寨卡病毒，可显著增强宿主的I型干扰素反应。我们推测Siba3在版纳绳蚋感染寨卡病毒后发挥着重要的抗病毒功能。为证实该推测，我们拟在IFNα/β受体缺陷小鼠和C57BL/6孕鼠感染模型中，明确Siba3对寨卡病毒感染导致的雄性不育和病毒母婴传播的抑制功能，明确Siba3是否抑制病毒感染诱导的炎症效应，阐明Siba3直接灭活病毒是否通过结合特定的病毒包膜蛋白、改变膜表面稳态并致其穿孔，阐明Siba3是否通过激活相关信号分子来增强宿主的I型干扰素反应。本课题将为版纳绳蚋抵御寨卡病毒的免疫防御策略提供创新性证据，并为防治寨卡病毒感染的多肽药物研发提供新型候选分子。

Blackflies are blood-sucking arthropods and serve as obligate vectors for many vector-borne diseases, including arborvirus-caused diseases. However, the mechanism of how blackfiles counteract with arborviruses remain unknown. In our preliminary research, S. bannaense was infected with Zika virus (ZIKV), and we found that Siba3, a host defence peptide of S. bannaense, was the most significantly up-regulated in the salivary gland post ZIKV infection. We further found that Siba3 potently inhibited ZIKV replication both in vitro and in vivo. Besides, Siba3 directly inactivated ZIKV. Additionally, Siba3 significantly enhanced the production of type I interferon in ZIKV RNA-stimulated mouse bone marrow-derived macrophages (BMDMs), and significantly enhanced the luciferase activity of pGL3-IFN-β in human 293T cells. On the basis of these findings, we presume that the most significant up-regulation of Siba3 in the salivary gland can potently restrict ZIKV infection in S. bannaense. To further understand the mechanism of action of Siba3 against ZIKV, we will investigate the effects of Siba3 on virus infection caused-male infertility in IFNα/β receptor-deficient mice, and mother-to-child transmission of ZIKV in pregnant C57BL/6 mice, and ZIKV infection-induced inflammatory response. We will investigate whether Siba3 can directly bind to virus particles, interact with specific membrane protein and in turn induce pore formation in ZIKV envelope membrane. We will understand how Siba3 regulate type I interferon (IFN) antiviral response of host. Hopefully, this project will provide innovative evidence for the immune defense strategy of S. bannaense against ZIKV, and provide a novel peptide candidate for the drug development against ZIKV infection.