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Letter
Nature 458, 1047-1050 (23 April 2009) | doi:10.1038/nature07967; Received 11 November 2008; Accepted 26 February 2009
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Scientist / Sr. Scientist - Biopharmaceutics
- Syngene International
- Bangalore, Karnataka 560099 India
Assistant Professor
- University of Texas
- Austin TX United States
Discovery of insect and human dengue virus host factors
October M. Sessions1,2, Nicholas J. Barrows2,3,4, Jayme A. Souza-Neto7, Timothy J. Robinson1,5,6, Christine L. Hershey8, Mary A. Rodgers8, Jose L. Ramirez7, George Dimopoulos7, Priscilla L. Yang8, James L. Pearson1,2,3 & Mariano A. Garcia-Blanco1,2,3,9
- Department of Molecular Genetics and Microbiology,
- Center for RNA Biology,
- Duke RNAi Facility,
- Institute for Genome Science and Policy,
- Medical Scientist Training Program,
- Program in Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
- 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
- Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
- Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169547
Correspondence to: James L. Pearson1,2,3Mariano A. Garcia-Blanco1,2,3,9 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 threat1, 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 identified3, 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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