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死灰复燃的全球重要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。基孔肯雅病毒引起的疾病是媒介传播疾病全球化的一个很好的例子，主要由埃及伊蚊和白纹伊蚊传播。在新的生态小生境中建立CHIKV传播周期的可能性与有能力的载体和易感人群是一个可信的威胁，必须认真对待。基孔肯雅病毒通过吸血时被感染的蚊子叮咬传播。苔藓唾液创造了一个特殊的免疫抑制皮肤微环境，促进感染和病毒传播的建立。我们最近发现，CHIKV感染的Ae.埃及伊蚊唾液在叮咬部位诱导TH2型反应，并抑制抗病毒因子IFN-γ和TLR-3。然而，这种具有受损的抗病毒效应子功能的免疫特权环境在CHIKV感染的建立和疾病进展中的意义尚未阐明。这将是我们所知的第一项研究，以调查Ae的作用。埃及人唾液在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，在从一个媒介-病原体关系的结果推断到另一个之前，我们研究更多的关联是至关重要的，这样我们就可以确定媒介-病毒-脊椎动物关系的潜在机制。拟议中的关于一种日益重要的病原体的工作，采用创新的办法和方法，是对我们关于这一主题的知识基础的重大贡献。 公共卫生相关性：在新的生态小生境中建立CHIKV传播周期的可能性与有能力的载体和易感人群是一个可信的威胁，必须认真对待。拟议的研究将促进对蚊子唾液在CHIKV传播和传播中的作用的理解。

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.