Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses

PLoS Pathogens

Erol Fikrig¹  Dana L. Vanlandingham¹  Gong Cheng²  Tonya M. Colpitts³  Jonathan Cox³  Sebastian Kurscheid³  Fabiana M. Feitosa³  Penghua Wang³  Manoj N. Krishnan³  Stephen Higgs³ 

[1] Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America;Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America;Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America

关键词: West Nile virus;    Mosquitoes;    Gene expression;    Flaviviruses;    Aedes aegypti;    Viral gene expression;    Microarrays;    Viral transmission;    infection;   

DOI  :  10.1371/journal.ppat.1002189

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

West Nile (WNV), dengue (DENV) and yellow fever (YFV) viruses are (re)emerging, mosquito-borne flaviviruses that cause human disease and mortality worldwide. Alterations in mosquito gene expression common and unique to individual flaviviral infections are poorly understood. Here, we present a microarray analysis of the Aedes aegypti transcriptome over time during infection with DENV, WNV or YFV. We identified 203 mosquito genes that were ≥5-fold differentially up-regulated (DUR) and 202 genes that were ≥10-fold differentially down-regulated (DDR) during infection with one of the three flaviviruses. Comparative analysis revealed that the expression profile of 20 DUR genes and 15 DDR genes was quite similar between the three flaviviruses on D1 of infection, indicating a potentially conserved transcriptomic signature of flaviviral infection. Bioinformatics analysis revealed changes in expression of genes from diverse cellular processes, including ion binding, transport, metabolic processes and peptidase activity. We also demonstrate that virally-regulated gene expression is tissue-specific. The overexpression of several virally down-regulated genes decreased WNV infection in mosquito cells and Aedes aegypti mosquitoes. Among these, a pupal cuticle protein was shown to bind WNV envelope protein, leading to inhibition of infection in vitro and the prevention of lethal WNV encephalitis in mice. This work provides an extensive list of targets for controlling flaviviral infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

【 授权许可】

CC BY