A Novel Virus that Infects & Sterilizes Insect Vectors of Human Disease

描述(申请人提供)：拟议的研究将提供一种新的病毒组-唾液腺肥大病毒(SGHV)的分子和生物学数据，它影响人类和动物疾病的昆虫媒介。目前，SGHV对病媒既有不利的影响，也有有利的影响。这种病毒在全世界所有采采蝇种群中(无症状地)存在，因此威胁到使用不育昆虫技术(SIT)来对抗人类非洲锥虫病和动物nagana的媒介。最近，国际原子能机构(原子能机构)认识到这一问题的严重性，资助了一个为期五年的项目，以消除大规模饲养设施中的这种病毒。另一方面，这种病毒迅速使雌性家蝇绝育，从而为开发基于生物学的节育方法来管理这种病媒提供了机会。SGHV是独一无二的；这些病毒感染成人，表现出高度的宿主和组织特异性，不影响宿主的生长和生存，但它们确实会使受感染的成年人绝育。此外，SGHV进化出了适合它们各自宿主的传播机制。家蝇SGHV通过食物的唾液污染传播。家蝇是一种r-战略家，在自然界中以高密度存在，并通过食用以前接触过受感染苍蝇的食物而很容易感染这种病毒。到目前为止，还没有垂直或性传播的证据；家蝇SGHV的生存依赖于大量环境稳定的、被包裹的病毒粒子的持续释放。或者，胎生采采蝇是一种k-战略家，在自然界中以相对较低的密度存在，在吸血过程中很少或根本不与同种蝇接触。除了唾液腺，采采蝇SGHV还会感染男性和女性的生殖组织，从而使性传播从男性传播到女性，并通过受感染的乳腺将母体传播给后代。具体目标将使用分子、生化和组织学方法相结合的方法来检查结构/功能关联，以检查家蝇SGHV的组成和病理。与原子能机构小组合作，将描述这一病毒组的比较生物学。这项探索性研究将为将SGHV用作家蝇节育和将副转基因基因转移到采采蝇中的媒介奠定基础，并为开发家蝇作为模型系统筛选抗病毒疗法和教授病毒生物学奠定基础。这项拟议的研究将描述一种新的病毒组，唾液腺肥大病毒(SGHV)，它感染人类和动物疾病的昆虫媒介。我们预计这项探索性研究将揭示这些DNA病毒在动物种群中复制和持续存在的机制。了解SGHs如何在采采蝇和普通家蝇的唾液腺中复制并关闭它们的繁殖，将为管理媒介种群开辟新的有效途径，并提供降低昆虫媒介能力的手段。

DESCRIPTION (provided by applicant): The proposed research will provide molecular and biological data on a novel virus group, the salivary gland hypertrophic viruses (SGHVs), which impacts insect vectors of both human and animal diseases. Presently, the SGHVs have both detrimental and beneficial impacts on disease vectors. This virus is established (asymptomatically) in all tsetse fly colonies worldwide and therefore threatens the use of sterile insect technologies (SIT) against vectors of both human African trypanosomiasis and animal nagana. Recently, the International Atomic Energy Agency (IAEA) recognized the severity of the problem by funding a five-year project to eliminate this virus from mass- rearing facilities. On the other hand, this virus rapidly sterilizes the female house fly, thus providing an opportunity to develop a biologically based birth control for managing this disease vector. SGHVs are unique; these viruses infect adults, display a high degree of host and tissue specificity, and do not impact growth and survival of the host, but they do sterilize infected adults. Furthermore, the SGHVs have evolved transmission mechanisms suited to their respective hosts. The house fly SGHV is transmitted via salivary contamination of food. The house fly, an r-strategist, exists in nature at high densities and readily picks up this virus by feeding on food previously exposed to infected flies. To date, there is no evidence of vertical or venereal transmission; survival of the house fly SGHV relies upon the continuous release of high numbers of environmentally stable, enveloped virions. Alternatively, the viviparous tsetse fly, a k-strategist, exists in nature at relatively low densities and has little or no contact with conspecifics during blood feeding. In addition to salivary glands, the tsetse fly SGHV infects male and female reproductive tissues, allowing venereal transmission from male to female and maternal transmission to progeny via infected milk glands. Specific objectives will examine the composition and pathology of house fly SGHV using a combination of molecular, biochemical, and histological methods to examine structure/function associations. In collaboration with the IAEA team, the comparative biology of this viral group will be delineated. This exploratory research will lay the foundation for utilizing the SGHVs as birth control for house flies and as vehicles to deliver paratransgenes into tsetse flies and for developing the house fly as a model system to screen antiviral therapies and to teach virus biology. The proposed research will characterize a novel virus group, the salivary gland hypertrophy viruses (SGHVs), which infect insect vectors of human and animal diseases. We expect that this exploratory research will reveal the mechanisms used by these DNA viruses to replicate and to persist in animal populations. Understanding how the SGHVs replicate in the salivary glands of tsetse flies and the common house fly and shut down their reproduction will open new, effective avenues for managing vector populations and provide the means to reduce the vector competence of insects.