1. Department of Molecular Genetics and Microbiology,
2. Center for RNA Biology,
3. Duke RNAi Facility,
4. Institute for Genome Science and Policy,
5. Medical Scientist Training Program,
6. Program in Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
7. Department of Molecular Microbiology and Immunology and Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205-2179, USA
8. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
9. Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169547

Correspondence to: James L. Pearson^1,2,3Mariano A. Garcia-Blanco^1,2,3,9 Correspondence and requests for materials should be addressed to J.L.P. (Email: pears016@mc.duke.edu) or M.A.G.-B. (Email: garci001@mc.duke.edu).

Abstract

Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection¹. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat^{1, 2}. 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^{3, 4, 5, 6, 7, 8, 9, 10}. 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 -glucosidases)^{3, 4, 5, 7, 9, 10}, 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.

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