Volume 90, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Dengue virus (DENV) is the most important mosquito-transmitted flavivirus that is transmitted throughout the tropical and subtropical regions of the world. The primary mosquito vector of DENV in urban locations is . Key to understanding the transmission of DENV is the relationship between pathogen and vector. Accordingly, we report our preliminary characterization of the differentially expressed proteins from mosquitoes after DENV infection. We investigated the virus–vector interaction through changes in the proteome of the salivary glands of mosquitoes with disseminated DENV serotype 2 (DENV-2) infections using two-dimensional gel electrophoresis and identification by mass spectrometry. Our findings indicate that DENV-2 infection in the salivary gland alters the expression of structural, secreted, and metabolic proteins. These changes in the salivary gland proteome highlight the virally influenced environment caused by a DENV-2 infection and warrant additional investigation to determine if these differences extend to the expectorated saliva.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Martina BE, Koraka P, Osterhaus AD, , 2009. Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22: 564581.[Crossref] [Google Scholar]
  2. Weaver SC, Reisen WK, , 2010. Present and future arboviral threats. Antiviral Res 85: 328345.[Crossref] [Google Scholar]
  3. Gubler DJ, , 2006. Dengue/dengue haemorrhagic fever: history and current status. Novartis Found Symp 277: 316.[Crossref] [Google Scholar]
  4. Jarman RG, Holmes EC, Rodpradit P, Klungthong C, Gibbons RV, Nisalak A, Rothman AL, Libraty DH, Ennis FA, Mammen MP, Jr Endy TP, , 2008. Microevolution of dengue viruses circulating among primary school children in Kamphaeng Phet, Thailand. J Virol 82: 54945500.[Crossref] [Google Scholar]
  5. Weaver SC, Vasilakis N, , 2009. Molecular evolution of dengue viruses: contributions of phylogenetics to understanding the history and epidemiology of the preeminent arboviral disease. Infect Genet Evol 9: 523540.[Crossref] [Google Scholar]
  6. Alto BW, Reiskind MH, Lounibos LP, , 2008. Size alters susceptibility of vectors to dengue virus infection and dissemination. Am J Trop Med Hyg 79: 688695. [Google Scholar]
  7. Alto BW, Lounibos LP, Mores CN, Reiskind MH, , 2008. Larval competition alters susceptibility of adult Aedes mosquitoes to dengue infection. Proc Biol Sci 275: 463471.[Crossref] [Google Scholar]
  8. Knox TB, Kay BH, Hall RA, Ryan PA, , 2003. Enhanced vector competence of Aedes aegypti (Diptera: Culicidae) from the Torres Strait compared with mainland Australia for dengue 2 and 4 viruses. J Med Entomol 40: 950956.[Crossref] [Google Scholar]
  9. Bennett KE, Olson KE, Munoz M de L, Fernandez-Salas I, Farfan-Ale JA, Higgs S, Black WC, 4th Beaty BJ, , 2002. Variation in vector competence for dengue 2 virus among 24 collections of Aedes aegypti from Mexico and the United States. Am J Trop Med Hyg 67: 8592. [Google Scholar]
  10. Black WC, 4th Bennett KE, Gorrochotegui-Escalante N, Barillas-Mury CV, Fernandez-Salas I, de Lourdes Munoz M, Farfan-Ale JA, Olson KE, Beaty BJ, , 2002. Flavivirus susceptibility in Aedes aegypti . Arch Med Res 33: 379388.[Crossref] [Google Scholar]
  11. Xi Z, Ramirez JL, Dimopoulos G, , 2008. The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog 4: e1000098.[Crossref] [Google Scholar]
  12. Fragkoudis R, Attarzadeh-Yazdi G, Nash AA, Fazakerley JK, Kohl A, , 2009. Advances in dissecting mosquito innate immune responses to arbovirus infection. J Gen Virol 90: 20612072.[Crossref] [Google Scholar]
  13. Sanchez-Vargas I, Travanty EA, Keene KM, Franz AW, Beaty BJ, Blair CD, Olson KE, , 2004. RNA interference, arthropod-borne viruses, and mosquitoes. Virus Res 102: 6574.[Crossref] [Google Scholar]
  14. Sanchez-Vargas I, Scott JC, Poole-Smith BK, Franz AW, Barbosa-Solomieu V, Wilusz J, Olson KE, Blair CD, , 2009. Dengue virus type 2 infections of Aedes aegypti are modulated by the mosquito's RNA interference pathway. PLoS Pathog 5: e1000299.[Crossref] [Google Scholar]
  15. Champagne DE, Smartt CT, Ribeiro JM, James AA, , 1995. The salivary gland-specific apyrase of the mosquito Aedes aegypti is a member of the 5′-nucleotidase family. Proc Natl Acad Sci USA 92: 694698.[Crossref] [Google Scholar]
  16. Valenzuela JG, Pham VM, Garfield MK, Francischetti IM, Ribeiro JM, , 2002. Toward a description of the sialome of the adult female mosquito Aedes aegypti . Insect Biochem Mol Biol 32: 11011122.[Crossref] [Google Scholar]
  17. Ribeiro JM, Arca B, Lombardo F, Calvo E, Phan VM, Chandra PK, Wikel SK, , 2007. An annotated catalogue of salivary gland transcripts in the adult female mosquito, Aedes aegypti . BMC Genomics 8: 6.[Crossref] [Google Scholar]
  18. Smartt CT, Kim AP, Grossman GL, James AA, , 1995. The Apyrase gene of the vector mosquito, Aedes aegypti, is expressed specifically in the adult female salivary glands. Exp Parasitol 81: 239248.[Crossref] [Google Scholar]
  19. Sim S, Ramirez JL, Dimopoulos G, , 2012. Dengue virus infection of the Aedes aegypti salivary gland and chemosensory apparatus induces genes that modulate infection and blood-feeding behavior. PLoS Pathog 8: e1002631.[Crossref] [Google Scholar]
  20. Almeras L, Fontaine A, Belghazi M, Bourdon S, Boucomont-Chapeaublanc E, Orlandi-Pradines E, Baragatti M, Corre-Catelin N, Reiter P, Pradines B, Fusai T, Rogier C, , 2010. Salivary gland protein repertoire from Aedes aegypti mosquitoes. Vector Borne Zoonotic Dis 10: 391402.[Crossref] [Google Scholar]
  21. Almeras L, Orlandi-Pradines E, Fontaine A, Villard C, Boucomont E, de Senneville LD, Baragatti M, Pascual A, Pradines B, Corre-Catelin N, Pages F, Reiter P, Rogier C, Fusai T, , 2009. Sialome individuality between Aedes aegypti colonies. Vector Borne Zoonotic Dis 9: 531541.[Crossref] [Google Scholar]
  22. Ribeiro JM, Francischetti IM, , 2003. Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives. Annu Rev Entomol 48: 7388.[Crossref] [Google Scholar]
  23. Ribeiro JM, , 1995. Blood-feeding arthropods: live syringes or invertebrate pharmacologists? Infect Agents Dis 4: 143152. [Google Scholar]
  24. Guo X, Xu Y, Bian G, Pike AD, Xie Y, Xi Z, , 2010. Response of the mosquito protein interaction network to dengue infection. BMC Genomics 11: 380.[Crossref] [Google Scholar]
  25. Wasinpiyamongkol L, Patramool S, Thongrungkiat S, Maneekan P, Sangmukdanan S, Misse D, Luplertlop N, , 2012. Protein expression in the salivary glands of dengue-infected Aedes aegypti mosquitoes and blood-feeding success. Southeast Asian J Trop Med Public Health 43: 13461357. [Google Scholar]
  26. Tchankouo-Nguetcheu S, Bourguet E, Lenormand P, Rousselle JC, Namane A, Choumet V, , 2012. Infection by chikungunya virus modulates the expression of several proteins in Aedes aegypti salivary glands. Parasit Vectors 5: 264.[Crossref] [Google Scholar]
  27. Chisenhall DM, Mores CN, , 2009. Diversification of West Nile virus in a subtropical region. Virol J 6: 106.[Crossref] [Google Scholar]
  28. Megy K, Emrich SJ, Lawson D, Campbell D, Dialynas E, Hughes DS, Koscielny G, Louis C, Maccallum RM, Redmond SN, Sheehan A, Topalis P, Wilson D, , 2012. VectorBase: improvements to a bioinformatics resource for invertebrate vector genomics. Nucleic Acids Res 40: D729D734.[Crossref] [Google Scholar]
  29. Bonizzoni M, Dunn WA, Campbell CL, Olson KE, Marinotti O, James AA, , 2012. Complex modulation of the Aedes aegypti transcriptome in response to dengue virus infection. PLoS One 7: e50512.[Crossref] [Google Scholar]
  30. Sim S, Dimopoulos G, , 2010. Dengue virus inhibits immune responses in Aedes aegypti cells. PLoS One 5: e10678.[Crossref] [Google Scholar]
  31. Dostert C, Jouanguy E, Irving P, Troxler L, Galiana-Arnoux D, Hetru C, Hoffmann JA, Imler JL, , 2005. The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila. Nat Immunol 6: 946953.[Crossref] [Google Scholar]
  32. Sabatier L, Jouanguy E, Dostert C, Zachary D, Dimarcq JL, Bulet P, Imler JL, , 2003. Pherokine-2 and -3. Eur J Biochem 270: 33983407.[Crossref] [Google Scholar]
  33. Mounsey A, Bauer P, Hope IA, , 2002. Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes. Genome Res 12: 770775.[Crossref] [Google Scholar]
  34. Platt KB, Linthicum KJ, Myint KS, Innis BL, Lerdthusnee K, Vaughn DW, , 1997. Impact of dengue virus infection on feeding behavior of Aedes aegypti . Am J Trop Med Hyg 57: 119125. [Google Scholar]
  35. Salazar MI, Richardson JH, Sanchez-Vargas I, Olson KE, Beaty BJ, , 2007. Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes. BMC Microbiol 7: 9.[Crossref] [Google Scholar]
  36. Lawson D, Arensburger P, Atkinson P, Besansky NJ, Bruggner RV, Butler R, Campbell KS, Christophides GK, Christley S, Dialynas E, Hammond M, Hill CA, Konopinski N, Lobo NF, MacCallum RM, Madey G, Megy K, Meyer J, Redmond S, Severson DW, Stinson EO, Topalis P, Birney E, Gelbart WM, Kafatos FC, Louis C, Collins FH, , 2009. VectorBase: a data resource for invertebrate vector genomics. Nucleic Acids Res 37: D583D587.[Crossref] [Google Scholar]
  37. Calvo E, Tokumasu F, Marinotti O, Villeval JL, Ribeiro JM, Francischetti IM, , 2007. Aegyptin, a novel mosquito salivary gland protein, specifically binds to collagen and prevents its interaction with platelet glycoprotein VI, integrin alpha2beta1, and von Willebrand factor. J Biol Chem 282: 2692826938.[Crossref] [Google Scholar]
  38. Rossingol PA, Spielman A, , 1982. Fluid transport across the ducts of a mosquito. J Insect Physiol 28: 579583.[Crossref] [Google Scholar]
  39. Peng Z, Simons FE, , 2007. Advances in mosquito allergy. Curr Opin Allergy Clin Immunol 7: 350354.[Crossref] [Google Scholar]
  40. Simons FE, Peng Z, , 2001. Mosquito allergy: recombinant mosquito salivary antigens for new diagnostic tests. Int Arch Allergy Immunol 124: 403405.[Crossref] [Google Scholar]
  41. Sylvestre G, Gandini M, Maciel-de-Freitas R, , 2013. Age-dependent effects of oral infection with dengue virus on Aedes aegypti (Diptera: Culicidae) feeding behavior, survival, oviposition success and fecundity. PLoS One 8: e59933.[Crossref] [Google Scholar]
  42. Ramirez JL, Dimopoulos G, , 2010. The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes. Dev Comp Immunol 34: 625629.[Crossref] [Google Scholar]
  43. Linthicum KJ, Platt K, Myint KS, Lerdthusnee K, Innis BL, Vaughn DW, , 1996. Dengue 3 virus distribution in the mosquito Aedes aegypti: an immunocytochemical study. Med Vet Entomol 10: 8792.[Crossref] [Google Scholar]
  44. Mackenzie J, , 2005. Wrapping things up about virus RNA replication. Traffic 6: 967977.[Crossref] [Google Scholar]
  45. Fernandez-Garcia MD, Mazzon M, Jacobs M, Amara A, , 2009. Pathogenesis of flavivirus infections: using and abusing the host cell. Cell Host Microbe 5: 318328.[Crossref] [Google Scholar]
  46. Jin JP, Chong SM, , 2010. Localization of the two tropomyosin-binding sites of troponin T. Arch Biochem Biophys 500: 144150.[Crossref] [Google Scholar]
  47. Ng ML, Hong SS, , 1989. Flavivirus infection: essential ultrastructural changes and association of Kunjin virus NS3 protein with microtubules. Arch Virol 106: 103120.[Crossref] [Google Scholar]
  48. Lyles DS, , 2000. Cytopathogenesis and inhibition of host gene expression by RNA viruses. Microbiol Mol Biol Rev 64: 709724.[Crossref] [Google Scholar]
  49. Hayes JD, Flanagan JU, Jowsey IR, , 2005. Glutathione transferases. Annu Rev Pharmacol Toxicol 45: 5188.[Crossref] [Google Scholar]
  50. Sheehan D, Meade G, Foley VM, Dowd CA, , 2001. Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J 360: 116.[Crossref] [Google Scholar]
  51. Gui Z, Hou C, Liu T, Qin G, Li M, Jin B, , 2009. Effects of insect viruses and pesticides on glutathione S-transferase activity and gene expression in Bombyx mori. J Econ Entomol 102: 15911598.[Crossref] [Google Scholar]
  52. Drakesmith H, Prentice A, , 2008. Viral infection and iron metabolism. Nat Rev Microbiol 6: 541552.[Crossref] [Google Scholar]

Data & Media loading...

Supplementary PDF

Supplementary table

  • Received : 15 Jul 2013
  • Accepted : 29 Oct 2013
  • Published online : 05 Mar 2014

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error