Volume 73, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The pre-membrane (prM) and envelope (E) genes of 41 viruses isolated from dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) patients from 1995 to 2002 were sequenced to determine the genetic variability of dengue 2 (DENV 2) viruses in the Philippines. The envelope sequence data were compared with a global sample of DENV 2 obtained from GenBank. Phylogenetic analysis revealed that two distinct genotypes, Asian 2 and Cosmopolitan, are currently circulating locally, each with the potential to cause severe hemorrhagic disease. After the initial isolation in 1998, the Cosmopolitan genotype has gradually and effectively replaced Asian genotype 2 in the Philippines. Members of this genotype were closely related to viruses from Australia, Singapore, and Thailand.


Article metrics loading...

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

Full text loading...



  1. World Health Organization, 2002. Dengue and dengue hemorrhagic fever. Fact sheet no. 117. Available at: http://www.who.int/mediacentre/factsheets/fs117/en/print.html
  2. Halstead SB, 1988. Pathogenesis of dengue: challenges to molecular biology. Science 239 : 476–481. [Google Scholar]
  3. Kliks SC, Nisalak A, Brandt WE, Wahl L, Burke DS, 1989. Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg 40 : 444–451. [Google Scholar]
  4. Thein S, Aung MM, Shwe TN, Aye M, Zaw A, Aye K, Aye KM, Aaskov J, 1997. Risk factors in dengue shock syndrome. Am J Trop Med Hyg 56 : 566–572. [Google Scholar]
  5. Barnes WJ, Rosen L, 1974. Fatal hemorrhagic disease and shock associated with primary dengue infection on a Pacific island. Am J Trop Med Hyg 23 : 495–506. [Google Scholar]
  6. Scott RM, Nimmannitya S, Bancroft WH, Mansuwan P, 1976. Shock syndrome in primary dengue infections. Am J Trop Med Hyg 25 : 866–874. [Google Scholar]
  7. Chungue E, Deubel V, Cassar O, Laille M, Martin PMV, 1993. Molecular epidemiology of dengue 3 viruses and genetic relatedness among dengue 3 strains isolated from patients with mild or severe form of dengue fever in French Polynesia. J Gen Virol 74 : 2765–2770. [Google Scholar]
  8. Rico-Hesse R, Harrison LM, Salas RA, Tovar D, Nisalak A, Ramos C, Boshell J, Meas MT, Nogueira RH, Rosa AT, 1997. Origins of dengue type 2 viruses associated with increased pathogenecity in the Americas. Virology 230 : 244–251. [Google Scholar]
  9. Gubler DG, Suharyano W, Lubis I, Eram S, Gunarso S, 1981. Epidemic dengue 3 in Central Java, associated with low viremia in man. Am J Trop Med Hyg 30 : 1094–1099. [Google Scholar]
  10. Leitmeyer KC, Vaughn DW, Watts DM, Salas R, Villalobos de Chacon I, Ramos C, Rico-Hesse R, 1999. Dengue virus structural differences that correlate with pathogenesis. J Virol 73 : 4738–4747. [Google Scholar]
  11. Pandey BD, Igarashi A, 2000. Severity-related molecular differences among nineteen strains of dengue type 2 viruses. Microbiol Immunol 44 : 179–188. [Google Scholar]
  12. Rico-Hesse R, 1990. Molecular evolution and distribution of dengue viruses type 1 and 2 in nature. Virology 174 : 479–493. [Google Scholar]
  13. Lewis JA, Chang G, Lanciotti RS, Kinney RM, Mayer LW, Trent DW, 1993. Phylogenetic relationships of dengue 2 viruses. Virology 197 : 216–224. [Google Scholar]
  14. Lanciotti RS, Lewis JG, Gubler DJ, Trent DW, 1994. Molecular evolution and epidemiology of dengue-3 viruses. J Gen Virol 75 : 65–75. [Google Scholar]
  15. Chungue E, Cassar O, Drouet MT, Guzman MG, Laile M, Rosen L, Deubel V, 1995. Molecular epidemiology of dengue-1 and dengue-4 viruses. J Gen Virol 76 : 1877–1884. [Google Scholar]
  16. Lanciotti RS, Gubler DJ, Trent DW, 1997. Molecular evolution and phylogeny of dengue 4 viruses. J Gen Virol 78 : 2279–2286. [Google Scholar]
  17. Twiddy SS, Farrar JJ, Nguyen VC, Wills B, Gould EA, Gritsun T, Lloyd G, Holmes EC, 2002. Phylogenetic relationships and differential selection pressures among genotypes of dengue 2 virus. Virology 298 : 63–72. [Google Scholar]
  18. Venzon EL, Rudnick A, Marchette NJ, Fable AE, Dukellis E, 1972. The greater Manila dengue hemorrhagic fever epidemic of 1966. J Phil Med Assoc 48 : 297–313. [Google Scholar]
  19. Hayes CG, Manaloto CR, Gonzales A, Ranoa CP, 1988. Dengue infections in the Philippines: clinical and virologic findings in 517 hospitalized patients. Am J Trop Med Hyg 39 : 110–116. [Google Scholar]
  20. Quintos FN, Lim LE, Juliano L, Reyes A, Lacson P, 1954. Hemorrhagic fever observed among children in the Philippines. Phil J Ped 3 : 1–19. [Google Scholar]
  21. Tayag EA, 1998. The dengue epidemic of 1998 in the Philippines. Den Bull 22. World Health Organization Regional Office for South-East Asia. Available at: http://w3.whosea.org/en/Section10/Section332/Section520_2421.htm.
  22. Matias RR, 2003. A historical review of dengue virus research in the Philippines. St. Luke’s J Med 1 : 3–8. [Google Scholar]
  23. Morita K, Tanaka M, Igarashi A, 1991. Rapid identification of dengue virus serotypes by using polymerase chain reaction. J Clin Mic 29 : 2107–2110. [Google Scholar]
  24. Igarashi A, Mohamed H, Yusof A, Sinniah M, Tanaka H, 1995. Production of type 2 dengue (D2) monoclonal antibody and cell culture derived D2 antigen for use in dengue IgM capture ELISA. Trop Med 37 : 165–173. [Google Scholar]
  25. Irie K, Mohan PM, Sasaguri Y, Putnak R, Padmanabhan R, 1989. Sequence analysis of cloned dengue virus type 2 genome (New Guinea C strain). Gene 75 : 197–211. [Google Scholar]
  26. Wang E, Ni H, Xu R, Barrett ADT, Watowich SJ, Gubler DJ, Weaver SC, 2000. Evolutionary relationships of endemic/epidemic and sylvatic dengue viruses. J Virol 74 : 3227–3234. [Google Scholar]
  27. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG, 1997. The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 24 : 4876–4882. [Google Scholar]
  28. Swofford DL, 1998. PAUP* 4.0 – Phylogenetic analysis using parsimony (*and other methods) 4.0b8. Sinauer Associates, Sutherland, MA.
  29. ter Meulen J, Grau M, Lenz O, Emmerich P, Schmidtz H, Oh F, Jaspert R, Niedrig M, 2000. Isolation and partial characterization of dengue virus type 2 and 4 strains from dengue fever and dengue haemorrhagic fever patients from Mindanao, Republic of the Philippines. Trop Med Int Health 5 : 325–329. [Google Scholar]
  30. Tokuda A, Sugito K, Tabeta H, Takasaki T, Yamada K, Kurane I, 2002. 3 dengue fever cases infected during a group tour to the Philippines. Kansenshogaku Zasshi 76 : 953–957. [Google Scholar]
  31. Dash PK, Parida MM, Saxena P, Kumar M, Rai A, Pasha ST, Jana AM, 2004. Emergence and continued circulation of dengue 2 (genotype IV) virus strains in northern India. J Med Virol 74 : 314–322. [Google Scholar]
  32. Foster JE, Bennett SN, Vaughan H, Vorndam V, McMillan WO, Carrington CV, 2003. Molecular evolution and phylogeny of dengue type 4 virus in the Caribbean. Virol 306 : 126–134. [Google Scholar]
  33. Singh UB, Maitra A, Broor S, Rai A, Pasha ST, Seth P, 1999. Partial nucleotide sequencing and molecular evolution of epidemic causing Dengue 2 strains. J Inf Dis 180 : 954–965. [Google Scholar]
  34. Trent DW, Grant JA, Rosen L, Monath TP, 1983. Genetic variation among dengue 2 viruses of different geographic origin. Virology 128 : 271–284. [Google Scholar]
  35. Uzcategui NY, Camacho D, Comach G, Cuello de Uzcategui R, Holmes EC, Gould EA, 2001. Molecular epidemiology of dengue type 2 virus in Venezuela: evidence for in situ virus evolution and recombination. J Gen Virol 82 : 2945–2953. [Google Scholar]
  36. Gubler DJ, Nalim S, Tan R, Saipan H, Sulianti SJ, 1979. Variation in susceptibility to oral infection with dengue viruses among geographic strains of Aedes aegypti. Am J Trop Med Hyg 45 : 644–651. [Google Scholar]
  37. Rosen L, Roseboom LE, Gubler DJ, Lien JC, Chaniotis BN, 1985. Comparative susceptibility of mosquito species and strains to oral and parenteral infection with dengue and Japanese encephalitis viruses. Am J Trop Med Hyg 34 : 603–615. [Google Scholar]
  38. Armstrong PM, Rico-Hesse R, 2003. Efficiency of dengue serotype 2 virus strains to infect and disseminate in Aedes aegypti. Am J Trop Med Hyg 68 : 539–544. [Google Scholar]
  39. Morens DM, Marchette NJ, Chu MC, Halstead SB, 1991. Growth of dengue type 2 virus isolates in human peripheral blood leukocytes correlates with severe and mild disease. Am J Trop Med Hyg 45 : 644–651. [Google Scholar]
  40. Wu SJ, Grouard-Vogel G, Mascola JR, Brachtel E, Putvana R, Louder MK, Filgueira L, Marovich MA, Wong HK, Blauvelt A, Murphy GS, Robb ML, Innes BL, Birx DL, Hayes CG, Frankel SS, 2000. Human skin Langerhans cells are targets of dengue virus infection. Nat Med 6 : 816–820. [Google Scholar]

Data & Media loading...

  • Received : 23 Mar 2005
  • Accepted : 01 Jun 2005

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