The Role of Mosquito Saliva in Chikungunya Virus Transmission and Dissemination

描述（由申请人提供）：蚊媒疾病是新出现和重新出现的具有全球重要性的疾病的一个很好的例子，在世界各地造成重大的公共卫生威胁。基孔肯雅病毒（CHIKV）引起的疾病是媒介传播疾病全球化的一个极好例子，主要由埃及伊蚊和白纹伊蚊传播。在具有有能力的病媒和易感人群的新生态位中建立CHIKV传播周期的可能性是一种可信的威胁，必须认真对待。基孔肯雅病毒是通过吸血时被感染蚊子叮咬传播的。蚊子唾液创造了一个特殊的免疫抑制皮肤微环境，促进了感染和病毒传播的建立。我们最近发现感染了chikv的伊蚊。埃及伊蚊唾液在叮咬部位诱导TH2型反应，抑制抗病毒因子IFN-和TLR-3。然而，这种具有抗病毒效应功能受损的免疫特权环境在建立CHIKV感染和疾病进展中的意义尚未阐明。这将是我们所知的第一个调查Ae的作用的研究。埃及伊蚊唾液在CHIKV传播和传播中的作用。根据以前的报告，很明显，蚊子唾液对病原体的影响可能是高度可变的，有时会增强感染，有时会产生保护作用。因此，在从一种病媒-病原体关系的结果推断到另一种病媒-病原体关系的结果之前，我们必须研究更多的关联，以便我们能够确定病媒-病毒-脊椎动物关系的潜在机制。关于一种日益重要的病原体的拟议工作，使用创新的方法和方法，对我们关于这一主题的知识库作出了重大贡献。

DESCRIPTION (provided by applicant): Mosquito-borne diseases are an excellent example of emerging and resurging diseases of global importance causing significant public health threats around the world. Disease caused by chikungunya virus (CHIKV) is an excellent example of globalization of a vector-borne disease, and is transmitted primarily by Aedes aegypti and Aedes albopictus. The potential for establishment of a CHIKV transmission cycle in new ecological niches with competent vectors and susceptible human population is a credible threat and must be treated seriously. Chikungunya virus is transmitted though the bite of an infected mosquito during blood feeding. Mosquito saliva creates a privileged immunosuppressed cutaneous microenvironment, that facilitates establishment of infection and virus dissemination. We have recently shown that CHIKV-infected Ae. aegypti saliva induces TH2 type response at the bite site, and suppressed antiviral factors IFN- and TLR-3. However, the implications of this immunologically privileged environment with impaired antiviral effector functions in the establishment of CHIKV infection and disease progression is not yet elucidated. This will be the first study to our knowledge to investigate the role of Ae. aegypti saliva in CHIKV transmission and dissemination. Based on previous reports, it is clear that the effects of mosquito saliva on a pathogen can be highly variable, sometimes enhancing infection and sometimes having a protective effect. As a consequence, before extrapolating from the results of one vector-pathogen relationship to another, it is critical that we study more associations so that we can identify the underlying mechanisms of the vector-virus-vertebrate relationship. The proposed work on an increasingly important pathogen, using innovative approaches and methodologies, represents a significant contribution to our knowledge base on this subject. PUBLIC HEALTH RELEVANCE: The potential for establishment of a CHIKV transmission cycle in new ecological niches with competent vectors and susceptible human population is a credible threat and must be treated seriously. Proposed studies will advance understanding of the effects of mosquito saliva in CHIKV transmission and dissemination.