title: Response of the mosquito protein interaction network to dengue infection.
abstract: BACKGROUND
  Two fifths of the world's population is at risk from dengue. The absence of effective drugs and vaccines leaves vector control as the primary intervention tool. Understanding dengue virus (DENV) host interactions is essential for the development of novel control strategies. The availability of genome sequences for both human and mosquito host greatly facilitates genome-wide studies of DENV-host interactions.
  
  
  RESULTS
  We developed the first draft of the mosquito protein interaction network using a computational approach. The weighted network includes 4,214 Aedes aegypti proteins with 10,209 interactions, among which 3,500 proteins are connected into an interconnected scale-free network. We demonstrated the application of this network for the further annotation of mosquito proteins and dissection of pathway crosstalk. Using three datasets based on physical interaction assays, genome-wide RNA interference (RNAi) screens and microarray assays, we identified 714 putative DENV-associated mosquito proteins. An integrated analysis of these proteins in the network highlighted four regions consisting of highly interconnected proteins with closely related functions in each of replication/transcription/translation (RTT), immunity, transport and metabolism. Putative DENV-associated proteins were further selected for validation by RNAi-mediated gene silencing, and dengue viral titer in mosquito midguts was significantly reduced for five out of ten (50.0%) randomly selected genes.
  
  
  CONCLUSIONS
  Our results indicate the presence of common host requirements for DENV in mosquitoes and humans. We discuss the significance of our findings for pharmacological intervention and genetic modification of mosquitoes for blocking dengue transmission.
authors.affiliation: Department of Entomology and Genetics Program, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.forename: Yao
authors.initials: Y
authors.lastname: Xu
authors.forename: Guowu
authors.initials: G
authors.lastname: Bian
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Pike
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xi
mesh_terms: D000330:Aedes / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D019295:Computational Biology; D030562:Databases, Protein; D003715:Dengue; D029721:Drosophila Proteins / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D017344:Genes, Insect / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D029701:Saccharomyces cerevisiae Proteins