Discovery of insect and human dengue virus host factors

October M. Sessions, Nicholas J. Barrows, Jayme A. Souza-Neto, Timothy J. Robinson, Christine L. Hershey, Mary A. Rodgers, Jose L. Ramirez, George Dimopoulos, Priscilla L. Yang, James L. Pearson, Mariano Garcia-Blanco

Research output: Contribution to journalArticle

266 Citations (Scopus)

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 α-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.

Original languageEnglish (US)
Pages (from-to)1047-1050
Number of pages4
JournalNature
Volume458
Issue number7241
DOIs
StatePublished - Apr 23 2009
Externally publishedYes

Fingerprint

Dengue Virus
Insects
Flavivirus
Dengue
Genome
Insect Vectors
Glucosidases
Double-Stranded RNA
Arthropods
Virus Diseases
Infection Control
RNA Interference
Drosophila melanogaster
Small Interfering RNA
Adenosine Triphosphatases
Vaccines
Public Health
Infection

ASJC Scopus subject areas

  • General

Cite this

Sessions, O. M., Barrows, N. J., Souza-Neto, J. A., Robinson, T. J., Hershey, C. L., Rodgers, M. A., ... Garcia-Blanco, M. (2009). Discovery of insect and human dengue virus host factors. Nature, 458(7241), 1047-1050. https://doi.org/10.1038/nature07967

Discovery of insect and human dengue virus host factors. / Sessions, October M.; Barrows, Nicholas J.; Souza-Neto, Jayme A.; Robinson, Timothy J.; Hershey, Christine L.; Rodgers, Mary A.; Ramirez, Jose L.; Dimopoulos, George; Yang, Priscilla L.; Pearson, James L.; Garcia-Blanco, Mariano.

In: Nature, Vol. 458, No. 7241, 23.04.2009, p. 1047-1050.

Research output: Contribution to journalArticle

Sessions, OM, Barrows, NJ, Souza-Neto, JA, Robinson, TJ, Hershey, CL, Rodgers, MA, Ramirez, JL, Dimopoulos, G, Yang, PL, Pearson, JL & Garcia-Blanco, M 2009, 'Discovery of insect and human dengue virus host factors', Nature, vol. 458, no. 7241, pp. 1047-1050. https://doi.org/10.1038/nature07967
Sessions OM, Barrows NJ, Souza-Neto JA, Robinson TJ, Hershey CL, Rodgers MA et al. Discovery of insect and human dengue virus host factors. Nature. 2009 Apr 23;458(7241):1047-1050. https://doi.org/10.1038/nature07967
Sessions, October M. ; Barrows, Nicholas J. ; Souza-Neto, Jayme A. ; Robinson, Timothy J. ; Hershey, Christine L. ; Rodgers, Mary A. ; Ramirez, Jose L. ; Dimopoulos, George ; Yang, Priscilla L. ; Pearson, James L. ; Garcia-Blanco, Mariano. / Discovery of insect and human dengue virus host factors. In: Nature. 2009 ; Vol. 458, No. 7241. pp. 1047-1050.
@article{48d56acf21304e15bbd72c5d513bf822,
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 α-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.",
author = "Sessions, {October M.} and Barrows, {Nicholas J.} and Souza-Neto, {Jayme A.} and Robinson, {Timothy J.} and Hershey, {Christine L.} and Rodgers, {Mary A.} and Ramirez, {Jose L.} and George Dimopoulos and Yang, {Priscilla L.} and Pearson, {James L.} and Mariano Garcia-Blanco",
year = "2009",
month = "4",
day = "23",
doi = "10.1038/nature07967",
language = "English (US)",
volume = "458",
pages = "1047--1050",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7241",

}

TY - JOUR

T1 - Discovery of insect and human dengue virus host factors

AU - Sessions, October M.

AU - Barrows, Nicholas J.

AU - Souza-Neto, Jayme A.

AU - Robinson, Timothy J.

AU - Hershey, Christine L.

AU - Rodgers, Mary A.

AU - Ramirez, Jose L.

AU - Dimopoulos, George

AU - Yang, Priscilla L.

AU - Pearson, James L.

AU - Garcia-Blanco, Mariano

PY - 2009/4/23

Y1 - 2009/4/23

N2 - 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 α-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.

AB - 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 α-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.

UR - http://www.scopus.com/inward/record.url?scp=65549169178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549169178&partnerID=8YFLogxK

U2 - 10.1038/nature07967

DO - 10.1038/nature07967

M3 - Article

VL - 458

SP - 1047

EP - 1050

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7241

ER -