the aedes aegypti toll pathway controls dengue virus infection埃及伊蚊人数通路控制登革热病毒感染.pdf

The Aedes aegypti Toll Pathway Controls Dengue Virus Infection ¤ Zhiyong Xi , Jose L. Ramirez, George Dimopoulos* W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America Abstract Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects’ innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an RNA interference–based defense system. We have used the recently released whole-genome sequence of the Ae. aegypti mosquito, in combination with high-throughput gene expression and RNA interference (RNAi)-based reverse genetic analyses, to characterize its response to dengue virus infection in different body compartments. We have further addressed the impact of the mosquito’s endogenous microbial flora on virus infection. Our findings indicate a significant role for the Toll pathway in regulating resistance to dengue virus, as indicated by an infection- responsive regulation and functional assessment of several Toll pathway–associated genes. We have also shown that the mosquito’s natural microbiota play a role in modulating the dengue virus infection, possibly through basal-level stimulation of the Toll immune pathway. Citation: Xi Z, Ramirez JL, Dimopoulos G (2008) The Aedes aegypti Toll Pathway Controls Dengue Virus Infection. PLoS Pathog 4(7): e1000098. doi:10.1371/ journal.ppat.1000098 Editor: David S. Schneider, Stanford University, United States of America Received February 15, 2008; Accepted June 6