title: Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses.
abstract: 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.
authors: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors: Tonya M
authors: TM
authors: Colpitts
authors: Jonathan
authors: J
authors: Cox
authors: Dana L
authors: DL
authors: Vanlandingham
authors: Fabiana M
authors: FM
authors: Feitosa
authors: Gong
authors: G
authors: Cheng
authors: Sebastian
authors: S
authors: Kurscheid
authors: Penghua
authors: P
authors: Wang
authors: Manoj N
authors: MN
authors: Krishnan
authors: Stephen
authors: S
authors: Higgs
authors: Erol
authors: E
authors: Fikrig
mesh_terms: D000330:Aedes / Q000235:genetics / Q000821:virology*; D000818:Animals; D002460:Cell Line; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D018177:Flavivirus Infections / Q000235:genetics / Q000517:prevention & control; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D019476:Insect Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D059467:Transcriptome / Q000235:genetics*; D014902:West Nile virus / Q000235:genetics / Q000502:physiology*; D015005:Yellow fever virus / Q000235:genetics / Q000502:physiology*
chemical_list: D019476:Insect Proteins