title: Discovery of insect and human dengue virus host factors.
abstract: Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and alpha-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: October M
authors.initials: OM
authors.lastname: Sessions
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Barrows
authors.forename: Jayme A
authors.initials: JA
authors.lastname: Souza-Neto
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Robinson
authors.forename: Christine L
authors.initials: CL
authors.lastname: Hershey
authors.forename: Mary A
authors.initials: MA
authors.lastname: Rodgers
authors.forename: Jose L
authors.initials: JL
authors.lastname: Ramirez
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
authors.forename: Priscilla L
authors.initials: PL
authors.lastname: Yang
authors.forename: James L
authors.initials: JL
authors.lastname: Pearson
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Garcia-Blanco
mesh_terms: D000330:Aedes / Q000235:genetics / Q000821:virology; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence / Q000235:genetics* / Q000502:physiology; D003716:Dengue Virus / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology / Q000821:virology*; D055785:Gene Knockdown Techniques; D049750:Genome, Insect / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007303:Insect Vectors / Q000235:genetics* / Q000502:physiology*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D012330:RNA, Double-Stranded