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

描述（由申请人提供）：拟议的研究将提供关于一种新型病毒组（唾液腺肥大病毒（SGHV））的分子和生物学数据，该病毒影响人类和动物疾病的昆虫媒介。目前，SGHV对病媒既有不利影响，也有有利影响。该病毒在全世界所有采采蝇种群中建立（无症状），因此威胁到使用昆虫不育技术（SIT）对抗人类非洲锥虫和动物长鼻病的载体。最近，国际原子能机构（原子能机构）认识到问题的严重性，资助了一个五年项目，从大量饲养设施中消除这种病毒。另一方面，这种病毒迅速使雌性家蝇绝育，从而提供了开发用于管理这种疾病媒介的基于生物学的生育控制的机会。SGHV是独一无二的;这些病毒感染成虫，表现出高度的宿主和组织特异性，并且不影响宿主的生长和存活，但它们确实使受感染的成虫绝育。此外，SGHV已经发展了适合其各自主机的传输机制。家蝇SGHV通过唾液污染食物传播。家蝇是一种r-strategist，在自然界中以高密度存在，通过进食先前接触过受感染苍蝇的食物，很容易感染这种病毒。迄今为止，没有证据表明存在垂直传播或性病传播;家蝇SGHV的生存依赖于大量环境稳定的包膜病毒粒子的持续释放。或者，胎生采采蝇，一种k-策略者，在自然界中以相对低的密度存在，并且在吸血期间很少或没有与同种接触。除唾液腺外，采采蝇SGHV还感染雄性和雌性生殖组织，允许通过感染的乳腺从雄性向雌性进行性传播和从母体向后代传播。具体目标将使用分子、生物化学和组织学方法的组合来检查家蝇SGHV的组成和病理，以检查结构/功能关联。将与原子能机构小组合作，对这一病毒群进行比较生物学研究。这项探索性研究将为利用SGHV作为家蝇的生育控制和作为将副转基因递送到采采蝇中的载体以及开发家蝇作为筛选抗病毒疗法和教授病毒生物学的模型系统奠定基础。拟议的研究将描述一个新的病毒组，唾液腺肥大病毒（SGHV），感染人类和动物疾病的昆虫载体。我们希望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SGHV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，将为管理病媒种群开辟新的有效途径，并提供降低昆虫病媒能力的手段。

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.