McElroy Kate L, Tsetsarkin Konstantin A, Vanlandingham Dana L, Higgs Stephen
Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, USA.
J Gen Virol. 2006 Oct;87(Pt 10):2993-3001. doi: 10.1099/vir.0.82023-0.
Live-attenuated virus vaccines are key components in controlling arboviral diseases, but they must not disseminate in or be transmitted by mosquito vectors. Although the cycles in which many mosquito-borne viruses are transmitted are well understood, the role of viral genetics in these processes has not been fully elucidated. Yellow fever virus (YFV) is an important arbovirus and the prototype member of the family Flaviviridae. Here, YFV was used in Aedes aegypti mosquitoes as a model to investigate the genetic basis of infection and dissemination in mosquitoes. Viruses derived from infectious clones and chimeric viruses with defined sequential manipulations were used to investigate the influence of specific sequences within the membrane and envelope structural protein genes on dissemination of virus from the mosquito midgut. Substitution of domain III of the envelope protein from a midgut-restricted YFV into a wild-type YFV resulted in a marked decrease in virus dissemination, suggesting an important role for domain III in this process. However, synergism between elements within the flavivirus structural and non-structural protein genes may be necessary for efficient virus escape from the mosquito midgut.
减毒活病毒疫苗是控制虫媒病毒疾病的关键组成部分，但它们绝不能在蚊媒中传播或通过蚊媒传播。尽管许多蚊媒病毒的传播周期已为人熟知，但病毒遗传学在这些过程中的作用尚未完全阐明。黄热病毒（YFV）是一种重要的虫媒病毒，也是黄病毒科的原型成员。在此，以埃及伊蚊为模型，利用YFV研究病毒在蚊子体内感染和传播的遗传基础。使用来自感染性克隆的病毒和经过特定序列操作的嵌合病毒，研究膜蛋白和包膜结构蛋白基因内特定序列对病毒从蚊子中肠传播的影响。将中肠受限型YFV包膜蛋白的结构域III替换为野生型YFV，导致病毒传播显著减少，表明结构域III在此过程中起重要作用。然而，黄病毒结构蛋白和非结构蛋白基因内元件之间的协同作用可能是病毒有效从中肠逃逸所必需的。
