Salivary Potentiation of Arboviral Infections

描述：(申请人提供)：一种虫媒病毒的可能性 感染发展并进展为有症状的，也许是致命的疾病， 当病毒通过节肢动物自然传播时，可能会大大增强 向量。病毒和媒介唾液腺物质可能被递送 皮肤上的。朗格汉斯细胞和树突状细胞因此很可能是 参与宿主对病毒和唾液物质的识别，以及抗原 呈递给巨噬细胞和T、B细胞。唾液的主要功能 产品是为了促进血液喂养，但它们也调节免疫力 分子。因此，唾液物质对相同的因素产生影响 确定虫媒病毒感染的结局。使用登革2型和西尼罗河 病毒及其各自的媒介(埃及伊蚊和淡色库蚊) 将针对三个具体目标：1)检查蚊子喂食的效果 唾液制剂对黄病毒易感C3H/HeJ小鼠病毒感染的影响 和抗黄病毒的C3H/RV小鼠；2)测定蚊虫的效果 摄食和唾液蛋白在宿主免疫系统的关键组件上 摄食/感染的部位和引流淋巴结；3)确定 虫媒病毒感染的唾液调节机制 在感染前给予中和抗唾液抗体，以及 通过操纵蚊子来改变特定唾液的表达水平 产品(S)。拟议的实验将使我们更好地理解 病毒-病媒-宿主相互作用，并将确定干预途径 控制虫媒病毒感染引起的传播和病理。这 知识可能有助于为人类开发小鼠模型 登革热感染。

DESCRIPTION: (provided by the applicant): The potential for an arboviral infection to develop and progress to symptomatic, and perhaps fatal disease, may be greatly enhanced when a virus is transmitted naturally by an arthropod vector. Viruses and vector salivary gland substances may be delivered cutaneously. Langerhans cells and dendritic cells are thus likely to be involved in host recognition of virus and salivary substances, and in antigen presentation to macrophages and T and B cells. The primary function of salivary products is to facilitate blood feeding, but they also modulate immune molecules. Salivary substances therefore impact upon the same factors that determine the outcome of arboviral infection. Using Dengue 2 and West Nile viruses with their respective vectors (Aedes aegypti and Culex pipiens) the PI will address three specific aims: 1) To examine the effect of mosquito feeding and salivary products on viral infection in flavivirus-susceptible C3H/HeJ mice and flavivirus-resistant C3H/RV mice; 2) To determine the effect of mosquito feeding and salivary proteins on key components of the host immune system at the site of feeding/infection and at their draining lymph nodes; 3) To define mechanisms involved in salivary modulation of arboviral infection via the administration of neutralizing anti-saliva antibodies prior to infection, and by manipulated mosquitoes to alter the expression levels of specific salivary product(s). Proposed experiments will lead to a better understanding of the virus-vector-host interactions and will identify avenues of intervention to control transmission and pathology resulting from arbovirus infections. This knowledge may contribute towards the development of a mouse model for human dengue infections.