EVOLUTIONARY CONSEQUENCES OF DENGUE VIRUS EMERGENCE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 蚊子传播的登革热病毒是登革热的病原体，是所有节肢动物传播病毒中对公众健康威胁最大的。登革病毒以两种不同的生命周期传播：（i）人类和居住区周围的伊蚊之间的全球流行性循环，以及（ii）西非和东南亚森林中树栖伊蚊和非人类灵长类之间的森林循环。 地方性病毒和森林病毒具有高度的遗传相似性，但森林病毒不会在人类中引起暴发。我们的研究重点是确定限制森林登革热病毒出现的障碍。 这一点特别重要，因为如果开发出有效的登革热疫苗，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毒株的竞争可以阻止森林病毒感染围居载体。我们用6种靶病毒株之一感染了埃及伊蚊（主要的围境传播媒介）：3种地方性登革热（血清2型）和3种森林登革热（血清2型）。 此外，每种靶菌株用于两种治疗之一：单一感染或与共同竞争者（登革热血清型4）混合、同时感染。 我们发现，每六个目标菌株的复制不受竞争的影响，因为在单一菌株感染的目标病毒浓度是没有不同的混合菌株感染。未来的研究将集中在竞争者的引入在时间上错开时的竞争结果。

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.