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.
Drosophila (fly)
Discovery of insect and human dengue virus host factors.” Nature, 458, 7241, Pp. 1047-50.Abstract
. 2009. “
Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia.” PLoS Genet, 6, 6, Pp. e1000994.Abstract
. 2010. “
Identification of genes that promote or antagonize somatic homolog pairing using a high-throughput FISH-based screen.” PLoS Genet, 8, 5, Pp. e1002667.Abstract
. 2012. “
Conserved regulators of nucleolar size revealed by global phenotypic analyses.” Sci Signal, 6, 289, Pp. ra70.Abstract
. 2013. “
Genome-wide RNAi screen for nuclear actin reveals a network of cofilin regulators.” J Cell Sci, 128, 13, Pp. 2388-400.Abstract
. 2015. “
Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection.” Science, 309, 5738, Pp. 1251-3.Abstract
. 2005. “
Quantitative morphological signatures define local signaling networks regulating cell morphology.” Science, 316, 5832, Pp. 1753-6.Abstract
. 2007. “
An analysis of normalization methods for Drosophila RNAi genomic screens and development of a robust validation scheme.” J Biomol Screen, 13, 8, Pp. 777-84.Abstract
. 2008. “
Building and analyzing protein interactome networks by cross-species comparisons.” BMC Syst Biol, 4, Pp. 36.Abstract
. 2010. “
Comparative RNAi screening identifies a conserved core metazoan actinome by phenotype.” J Cell Biol, 194, 5, Pp. 789-805.Abstract
. 2011. “
Genetic determinants of phosphate response in Drosophila.” PLoS One, 8, 3, Pp. e56753.Abstract
. 2013. “
A functional genomic analysis of cell morphology using RNA interference.” J Biol, 2, 4, Pp. 27.Abstract
. 2003. “
Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity.” Proc Natl Acad Sci U S A, 103, 24, Pp. 9357-62.Abstract
. 2006. “
Cellular phenotype recognition for high-content RNA interference genome-wide screening.” J Biomol Screen, 13, 1, Pp. 29-39.Abstract
. 2008. “