Alterations in the Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses

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West Nile (WNV), dengue (DENV) and yellow fever (YFV) viruses are (re)emerging, mosquito-borne flaviviruses that cause human disease and mortality worldwide. Alterations in mosquito gene expression common and unique to individual flaviviral infections are poorly understood. Here, we present a microarray analysis of the Aedes aegypti transcriptome over time during infection with DENV, WNV or YFV. We identified 203 mosquito genes that were ≥5-fold differentially up-regulated (DUR) and 202 genes that were ≥10-fold differentially down-regulated (DDR) during infection with one of the three flaviviruses. Comparative analysis revealed that the expression profile of 20 DUR genes and 15 DDR genes was quite similar between the three flaviviruses on D1 of infection, indicating a potentially conserved transcriptomic signature of flaviviral infection. Bioinformatics analysis revealed changes in expression of genes from diverse cellular processes, including ion binding, transport, metabolic processes and peptidase activity. We also demonstrate that virally-regulated gene expression is tissue-specific. The overexpression of several virally down-regulated genes decreased WNV infection in mosquito cells and Aedes aegypti mosquitoes. Among these, a pupal cuticle protein was shown to bind WNV envelope protein, leading to inhibition of infection in vitro and the prevention of lethal WNV encephalitis in mice. This work provides an extensive list of targets for controlling flaviviral infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

Vyšlo v časopise: Alterations in the Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002189
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002189

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1. MackenzieJSGublerDJPetersenLR 2004 Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 10 S98 109

2. RappoleJHDerricksonSRHubalekZ 2000 Migratory birds and spread of West Nile virus in the Western Hemisphere. Emerg Infect Dis 6 319 328

3. GublerDJ 2002 Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol 10 100 103

4. sitePAHOw 2007 Number of reported cases of dengue and dengue hemorrhagic fever (DHF) in the Americas, by country: figures for 2007

5. BlairCDAdelmanZNOlsonKE 2000 Molecular strategies for interrupting arthropod-borne virus transmission by mosquitoes. Clin Microbiol Rev 13 651 661

6. BaeHGDrostenCEmmerichPColebundersRHantsonP 2005 Analysis of two imported cases of yellow fever infection from Ivory Coast and The Gambia to Germany and Belgium. J Clin Virol 33 274 280

7. TomoriO 2004 Yellow fever: the recurring plague. Crit Rev Clin Lab Sci 41 391 427

8. MonathTP 2006 Yellow fever as an endemic/epidemic disease and priorities for vaccination. Bull Soc Pathol Exot 99 341 347

9. Souza-NetoJASimSDimopoulosG 2009 An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc Natl Acad Sci U S A 106 17841 17846

10. XiZRamirezJLDimopoulosG 2008 The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog 4 e1000098

11. SessionsOMBarrowsNJSouza-NetoJARobinsonTJHersheyCL 2009 Discovery of insect and human dengue virus host factors. Nature 458 1047 1050

12. Bartholomay LC, Waterhouse RM, Mayhew GF, Campbell CL, Michel K, et al. Pathogenomics of Culex quinquefasciatus and meta-analysis of infection responses to diverse pathogens. Science 330 88 90

13. ChengGCoxJWangPKrishnanMNDaiJ 2010 A C-type lectin collaborates with a CD45 phosphatase homolog to facilitate West Nile virus infection of mosquitoes. Cell 142 714 725

14. Molina-CruzAGuptaLRichardsonJBennettKBlackWt 2005 Effect of mosquito midgut trypsin activity on dengue-2 virus infection and dissemination in Aedes aegypti. Am J Trop Med Hyg 72 631 637

15. Baron OL, Ursic-Bedoya RJ, Lowenberger CA, Ocampo CB Differential gene expression from midguts of refractory and susceptible lines of the mosquito, Aedes aegypti, infected with Dengue-2 virus. J Insect Sci 10 41

16. SmarttCTRichardsSLAndersonSLEricksonJS 2009 West Nile virus infection alters midgut gene expression in Culex pipiens quinquefasciatus Say (Diptera: Culicidae). Am J Trop Med Hyg 81 258 263

17. BennettKEFlickDFlemingKHJochimRBeatyBJ 2005 Quantitative trait loci that control dengue-2 virus dissemination in the mosquito Aedes aegypti. Genetics 170 185 194

18. SimSDimopoulosG 2010 Dengue virus inhibits immune responses in Aedes aegypti cells. PLoS One 5 e10678

19. BrackneyDEFoyBDOlsonKE 2008 The effects of midgut serine proteases on dengue virus type 2 infectivity of Aedes aegypti. Am J Trop Med Hyg 79 267 274

20. GouldEASolomonT 2008 Pathogenic flaviviruses. Lancet 371 500 509

21. NeneVWortmanJRLawsonDHaasBKodiraC 2007 Genome sequence of Aedes aegypti, a major arbovirus vector. Science 316 1718 1723

22. VanlandinghamDLMcGeeCEKlingerKAVesseyNFredregilloC 2007 Relative susceptibilties of South Texas mosquitoes to infection with West Nile virus. Am J Trop Med Hyg 77 925 928

23. CDC 2009 http://www.cdc.gov/ncidod/dvbid/westnile/mosquitoSpecies.htm

24. GauntMWSallAAde LamballerieXFalconarAKDzhivanianTI 2001 Phylogenetic relationships of flaviviruses correlate with their epidemiology, disease association and biogeography. J Gen Virol 82 1867 1876

25. SandersHRFoyBDEvansAMRossLSBeatyBJ 2005 Sindbis virus induces transport processes and alters expression of innate immunity pathway genes in the midgut of the disease vector, Aedes aegypti. Insect Biochem Mol Biol 35 1293 1307

26. WangTTownTAlexopoulouLAndersonJFFikrigE 2004 Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 10 1366 1373

27. IsoeJKunzSManhartCWellsMAMiesfeldRL 2007 Regulated expression of microinjected DNA in adult Aedes aegypti mosquitoes. Insect Mol Biol 16 83 92

28. HiggsSSnowKGouldEA 2004 The potential for West Nile virus to establish outside of its natural range: a consideration of potential mosquito vectors in the United Kingdom. Trans R Soc Trop Med Hyg 98 82 87

29. HubalekZHalouzkaJ 1999 West Nile fever--a reemerging mosquito-borne viral disease in Europe. Emerg Infect Dis 5 643 650

30. DubrovskyEBDubrovskayaVABilderbackALBergerEM 2000 The isolation of two juvenile hormone-inducible genes in Drosophila melanogaster. Dev Biol 224 486 495

31. WeiHZhouMM 2010 Viral-encoded enzymes that target host chromatin functions. Biochim Biophys Acta 1799 296 301

32. KentJRZengPYAtanasiuDGardnerJFraserNW 2004 During lytic infection herpes simplex virus type 1 is associated with histones bearing modifications that correlate with active transcription. J Virol 78 10178 10186

33. PengZXuWJamesAALamHSunD 2001 Expression, purification, characterization and clinical relevance of rAed a 1--a 68-kDa recombinant mosquito Aedes aegypti salivary allergen. Int Immunol 13 1445 1452

34. Hess AM, Prasad AN, Ptitsyn A, Ebel GD, Olson KE, et al. Small RNA profiling of Dengue virus-mosquito interactions implicates the PIWI RNA pathway in anti-viral defense. BMC Microbiol 11 45

35. ArnotCJGayNJGangloffM 9509 Molecular mechanism that induces activation of Spatzle, the ligand for the Drosophila Toll receptor. J Biol Chem 285 19502 19509

36. KrishnanMNNgASukumaranBGilfoyFDUchilPD 2008 RNA interference screen for human genes associated with West Nile virus infection. Nature 455 242 245

37. BolstadBMIrizarryRAAstrandMSpeedTP 2003 A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19 185 193

38. Xu WW, Carter CJ Parallel multiplicity and error discovery rate (EDR) in microarray experiments. BMC Bioinformatics 11 465

39. Huang daWShermanBTLempickiRA 2009 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4 44 57

40. DennisGJrShermanBTHosackDAYangJGaoW 2003 DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 4 P3