EVOLUTIONARY CONSEQUENCES OF DENGUE VIRUS EMERGENCE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 蚊媒登革热病毒是登革热的病原体，在所有节肢动物传播的病毒中，它对公众健康构成了最大的威胁。登革热病毒在两个不同的生命周期中循环：(1)在人类和周围型伊蚊之间的全球地方性循环；(2)在西非和东南亚森林中在树栖伊蚊和非人类灵长类之间的一个亚热带循环。地方性病毒和地方性病毒表现出很高的遗传相似性，但地方性病毒不会在人类中引起疫情。我们的研究重点是找出限制登革热病毒出现的障碍。这一点尤其重要，因为如果开发出一种有效的登革热疫苗，这些障碍就可以消除。目前的研究验证了这样一个假设，即来自已建立的地方性毒株的竞争可以防止海岛病毒感染牙周炎病媒。我们用6株目标病毒株之一感染埃及伊蚊，埃及伊蚊是主要的牙周病媒介，其中3株是地方性登革热(血清2型)，3株是地方性登革热(血清2型)。此外，每个目标菌株用于两种治疗之一：单独感染或与共同竞争对手(登革热血清4型)混合并发感染。我们发现，由于单一菌株感染的目标病毒浓度与混合菌株感染的目标病毒浓度没有区别，因此六个目标菌株的复制都不受竞争的影响。未来的研究将集中在当竞争对手的引入在时间上交错时的竞争结果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mosquito-transmitted dengue virus, the agent of dengue fever, poses the most significant threat to public health of any arthropod-borne virus. Dengue viruses circulate in two distinct life cycles: (i) a global endemic cycle between humans and peridomestic Aedes mosquitoes, and (ii) a sylvatic cycle in the forests of West Africa and southeast Asia between arboreal Aedes mosquitoes and non-human primates. Endemic and sylvatic viruses show high genetic similarity, but sylvatic viruses do not cause outbreaks in humans. Our research has focused on identifying the barriers that limit the emergence of sylvatic dengue viruses. This is particularly important because if an effective dengue vaccine were developed, such barriers could come down. The current study tested the hypothesis that competition from established endemic strains could prevent sylvatic viruses from infecting peridomestic vector. We infected groups of Aedes aegypti, the major peridomestic vector, with one of 6 target virus strains: 3 strains of endemic dengue (serotype 2) and 3 strains of sylvatic dengue (serotype 2). Moreover each target strain was used in one of two treatments: single infection or mixed, concurrent infection with a common competitor (dengue serotype 4). We found that replication of each of the six target strains was unaffected by competition, since target virus concentration in the single-strain infections was not different from that of the mixed-strain infections. Future research will focus on the outcome of competition when the introduction of competitors is staggered in time.