Volume 101, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular characteristics of the dengue virus (DENV) is required. In 2014, we isolated the virus from patients and sequenced its genome. The sequences of DENV isolated from Guangdong and other countries screened since 2005 were studied to establish molecular evolutionary databases along with epidemiological data to explore its epidemiological, phylogenetic, and molecular characteristics. Causes underlying the occurrence of the dengue epidemic included importation and localization of the virus. The number of indigenous cases significantly exceeded that of imported cases. Dengue virus 1 is the most important serotype and caused the long-term epidemic locally. Based on the data available since 2005, DENV1 was divided into three genotypes (I, IV, and V). Only genotypes I and V were detected in 2014. In 2014, an epidemic involving old lineages of DENV1 genotype V occurred after 2 years of silence. The genotype was previously detected from 2009 to 2011. Genotype I, which caused recent epidemics, demonstrated a continuation of new lineages, and a predictive pattern of molecular evolution since 2005 among the four lineages was present. The DENV isolated from Guangdong was closely related to those causing large-scale epidemics in neighboring countries, suggesting the possibility of its import from these countries. The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Article metrics loading...

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

Full text loading...



  1. Simmons CP, Farrar JJ, Chau VVN, Wills B, , 2012. Dengue. New Engl J Med 366: 14231432. [Google Scholar]
  2. Guhasapir D, Schimmer B, , 2005. Dengue fever: new paradigms for a changing epidemiology. Emerg Themes Epidemiol 2: 1. [Google Scholar]
  3. Peng HJ, 2012. A local outbreak of dengue caused by an imported case in Dongguan China. BMC Public Health 12: 83. [Google Scholar]
  4. Nogueira RMR, Araújo JMGD, Schatzmayr HG, , 2007. Dengue viruses in Brazil, 1986–2006. Rev Panam Salud Pública 22: 358363. [Google Scholar]
  5. WHO, 2009. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control, New ed., Vol. 6. Geneva, Switzerland: World Health Organization, 990. [Google Scholar]
  6. World Health Organization, 2019. Dengue and Severe Dengue. Available at: http://www.who.int/mediacentre/factsheets/fs117/en/. [Google Scholar]
  7. Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG, Moyes CL, Farlow AW, Scott TW, Hay SI, , 2012. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis 6: e1760. [Google Scholar]
  8. Bhatt S, 2013. The global distribution and burden of dengue. Nature 496: 504507. [Google Scholar]
  9. Chambers TJ, Chang SH, Galler R, Rice CM, , 1990. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44: 649688. [Google Scholar]
  10. Holmes EC, Twiddy SS, , 2003. The origin, emergence and evolutionary genetics of dengue virus. Infect Genet Evol 3: 1928. [Google Scholar]
  11. De BF, Nogueira RM, Faria NR, Simões JB, Nunes PC, de Filippis AM, dos Santos FB, , 2015. Insights of the genetic diversity of DENV-1 detected in Brazil in 25 years: analysis of the envelope domain III allows lineages characterization. Infect Genet Evol 34: 126136. [Google Scholar]
  12. Rico-Hesse R, , 2003. Microevolution and virulence of dengue viruses. Adv Virus Res 59: 315341. [Google Scholar]
  13. Penny D, 1994. The role of models in reconstructing evolutionary trees. Syst Assoc Spec 52: 211. [Google Scholar]
  14. Lanciotti RS, Gubler DJ, Trent DW, , 1997. Molecular evolution and phylogeny of dengue-4 viruses. J Gen Virol 78: 22792286. [Google Scholar]
  15. Jackowiak P, Kuls K, Budzko L, Mania A, Figlerowicz M, Figlerowicz M, , 2014. Phylogeny and molecular evolution of the hepatitis C virus. Infect Genet Evol 21: 6772. [Google Scholar]
  16. Xu J, Zhong HA, Madrahimov A, Helikar T, Lu G, , 2014. Molecular phylogeny and evolutionary dynamics of influenza A nonstructural (NS) gene. Infect Genet Evol 22: 192200. [Google Scholar]
  17. Morenoaltamirano MM, Sánchezgarcía FJ, Muñoz ML, , 2002. Non Fc receptor-mediated infection of human macrophages by dengue virus serotype 2. J Gen Virol 83: 11231130. [Google Scholar]
  18. Gualano RC, Pryor MJ, Cauchi MR, Wright PJ, Davidson AD, , 1998. Identification of a major determinant of mouse neurovirulence of dengue virus type 2 using stably cloned genomic-length cDNA. J Gen Virol 79: 437446. [Google Scholar]
  19. Klungthong C, Putnak R, Mammen MP, Li T, Zhang C, , 2008. Molecular genotyping of dengue viruses by phylogenetic analysis of the sequences of individual genes. J Virol Methods 154: 175181. [Google Scholar]
  20. Wu JY, Lun ZR, James AA, Chen XG, , 2010. Dengue fever in mainland China. Am J Trop Med Hyg 83: 664671. [Google Scholar]
  21. Liu C, Liu Q, Lin H, Xin B, Nie J, , 2014. Spatial analysis of dengue fever in Guangdong province, China, 2001–2006. Asia Pac J Public Health 26:5866. [Google Scholar]
  22. He JF, Luo HM, Liang WJ, Zheng K, Kang M, Liu LP, , 2007. Epidemic situation of dengue fever in Guangdong province, China, 1990–2005. Dengue Bull 31: 19. [Google Scholar]
  23. Wu W, 2011. Molecular epidemiology of dengue viruses in southern China from 1978 to 2006. Virol J 8: 19. [Google Scholar]
  24. Guo R, 2014. The prevalence and endemic nature of dengue infections in Guangdong, south China: an epidemiological, serological, and etiological study from 2005–2011. PLoS One 9: e85596. [Google Scholar]
  25. Xiao JP, 2016. Characterizing a large outbreak of dengue fever in Guangdong province, China. Infect Dis Poverty 5: 44. [Google Scholar]
  26. Huang L, 2016. Epidemiology and characteristics of the dengue outbreak in Guangdong, southern China, in 2014. Eur J Clin Microbiol Infect Dis 35: 269277. [Google Scholar]
  27. Burland TG, , 2000. DNASTAR’s Lasergene sequence analysis software. Methods Mol Biol 132: 7191. [Google Scholar]
  28. Altschul SF, , 1990. Basic local alignment search tool (BLAST). J Mol Biol 215: 403410. [Google Scholar]
  29. Hall TA, , 1999. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41: 9598. [Google Scholar]
  30. Kumar S, Tamura K, Nei M, , 1994. MEGA: molecular evolutionary genetics analysis software for microcomputers. Comput Appl Biosci 10: 189191. [Google Scholar]
  31. Prasanth GK, Divya LM, Sadasivan C, , 2010. Bisphenol-A can bind to human glucocorticoid receptor as an agonist: an in silicostudy. J Appl Toxicol 30: 769774. [Google Scholar]
  32. Luo H, He J, Zheng K, Li L, Jiang L, , 2002. Analysis on the epidemiologic features of dengue fever in Guangdong province, 1990–2000. Chin J Epidemiol 23: 427430. [Google Scholar]
  33. Liang WJ, 2007. Epidemiologlcal analysis of dengue fever in Guangdong province, 2001–2006. South China J Prev Med 33:47. [Google Scholar]
  34. Chen S, , 2011. The origin of dengue viruses caused the DF outbreak in Guangdong province, China, in 2006. Infect Genet Evol 11: 11831187. [Google Scholar]
  35. Zheng K, Zhou HQ, Yan J, Ke CW, Maeda A, Maeda J, Takashima I, Kurane I, Ma H, Xie XM, , 2009. Molecular characterization of the, E gene of dengue virus type 1 isolated in Guangdong province, China, in 2006. Epidemiol Infect 137: 7378. [Google Scholar]
  36. Luo L, Liang HY, Hu YS, Liu WJ, Wang YL, Jing QL, Zheng XL, Yang ZC, , 2012. Epidemiological, virological, and entomological characteristics of dengue from 1978 to 2009 in Guangzhou, China. J Vector Ecol 37: 230240. [Google Scholar]
  37. Runge-Ranzinger S, Mccall PJ, Kroeger A, Horstick O, , 2014. Dengue disease surveillance: an updated systematic literature review. Trop Med Int Health 19: 11161160. [Google Scholar]
  38. Huang L, 2016. Epidemiology and characteristics of the dengue outbreak in Guangdong, southern China, in 2014. Eur J Clin Microbiol Infect Dis 35: 269277. [Google Scholar]
  39. Pei W, 2016. Molecular characterization and phylogenetic analysis of dengue virus type 1 in Guangdong in 2014. Springerplus 5: 1942. [Google Scholar]
  40. Li MT, Sun GQ, Yakob L, Zhu HP, Jin Z, Zhang WY, , 2016. The driving force for 2014 dengue outbreak in Guangdong, China. PLoS One 11: e0166211. [Google Scholar]
  41. Shen SQ, 2015. Multiple sources of infection and potential endemic characteristics of the large outbreak of dengue in Guangdong in 2014. Sci Rep 5: 16913. [Google Scholar]
  42. Geng L, 2017. Molecular epidemiology demonstrates that imported and local strains circulated during the 2014 dengue outbreak in Guangzhou, China. Virol Sin 32: 6372. [Google Scholar]
  43. Mendez JA, Usmeciro JA, Domingo C, Rey GJ, Sanchez JA, Tenorio A, Gallego-Gomez JC, , 2010. Phylogenetic history demonstrates two different lineages of dengue type 1 virus in Colombia. Virol J 7: 226. [Google Scholar]
  44. Drumond BP, Mondini A, Schmidt DJ, Bosch I, Nogueira ML, , 2012. Population dynamics of DENV-1 genotype V in Brazil is characterized by co-circulation and strain/lineage replacement. Arch Virol 157: 20612073. [Google Scholar]
  45. Cunha MD, Guimarães VN, Souza M, de Paula Cardoso Dd, de Almeida TN, de Oliveira TS, Fiaccadori FS, , 2016. Phylodynamics of DENV-1 reveals the spatiotemporal co-circulation of two distinct lineages in 2013 and multiple introductions of dengue virus in Goiás, Brazil. Infect Genet Evol 43: 130134. [Google Scholar]
  46. Lee KS, Lo S, Tan SS, Chua R, Tan LK, Xu H, Ng LC, , 2012. Dengue virus surveillance in Singapore reveals high viral diversity through multiple introductions and in situ, evolution. Infect Genet Evol 12: 7785. [Google Scholar]
  47. Rajarethinam J, 2018. Dengue in Singapore from 2004 to 2016: cyclical epidemic patterns dominated by serotypes 1 and 2. Am J Trop Med Hyg 99: 204210. [Google Scholar]
  48. Zheng K, Zhou HQ, Yan J, Ke CW, Maeda A, Maeda J, Takashima I, Kurane I, Ma H, Xie XM, , 2009. Molecular characterization of the E gene of dengue virus type 1 isolated in Guangdong province, China, in 2006. Epidemiol Infect 137: 7378. [Google Scholar]
  49. Chen S, , 2011. The origin of dengue viruses caused the DF outbreak in Guangdong province, China, in 2006. Infect Genet Evol 11: 11831187. [Google Scholar]
  50. Fan JC, Lin HL, Wu HX, Wang J, Yang SR, Liu QY, 2013. Spatial and temporal distribution characteristics of dengue fever in Guangdong province, China during 2006–2011. Chin J Vector Biol Control 24: 389391. [Google Scholar]
  51. Guo R, Peng Z, Song T, He J, Zhong H, Li L, Liang W, , 2014. Current infection status and epidemic risk analysis of dengue fever and chikungunya in Guangdong province, from 1990 to 2012. Zhonghua Liu Xing Bing Xue Za Zhi 35: 167169. [Google Scholar]
  52. Feng L, 2018. Distribution of dengue virus serum type I in Guangdong, 2013–2016. Mod Prev Med 45: 38573961. [Google Scholar]
  53. Jiufeng S, 2018. The epidemiological characteristics and molecular phylogeny of the dengue virus in Guangdong, China, 2015. Sci Rep 8: 9976. [Google Scholar]
  54. Zhijun B, 2018. Evolutionary and phylodynamic analyses of, dengue virus, serotype I in Guangdong province, China, between 1985 and 2015. Virus Res 256: 201208. [Google Scholar]
  55. Fahri S, Yohan B, Trimarsanto H, Sayono S, Hadisaputro S, Dharmana E, Syafruddin D, Sasmono RT, , 2013. Molecular surveillance of dengue in semarang, Indonesia revealed the circulation of an old genotype of dengue virus serotype-1. PLoS Negl Trop Dis 7: e2354. [Google Scholar]
  56. Kotaki T, Yamanaka A, Mulyatno KC, Churrotin S, Labiqah A, Sucipto TH, Soegijanto S, Kameoka M, Konishi E, , 2014. Continuous dengue type 1 virus genotype shifts followed by co-circulation, clade shifts and subsequent disappearance in Surabaya, Indonesia, 2008–2013. Infect Genet Evol 28: 4854. [Google Scholar]
  57. Castonguay-Vanier J, 2018. Molecular epidemiology of dengue viruses in three provinces of Lao PDR, 2006–2010. PLoS Negl Trop Dis 12: e0006203. [Google Scholar]
  58. Moore PR, Hurk AFVD, Mackenzie JS, Pyke AT, , 2017. Dengue viruses in Papua New Guinea: evidence of endemicity and phylogenetic variation, including the evolution of new genetic lineages. Emerg Microbes Infect 6: e114. [Google Scholar]
  59. Ocazionez RE, Cortés FM, Villar LA, Gómez SY, , 2006. Temporal distribution of dengue virus serotypes in Colombian endemic area and dengue incidence. Re-introduction of dengue-3 associated to mild febrile illness and primary infection. Mem Inst Oswaldo Cruz 101: 725731. [Google Scholar]
  60. Ocazionez RE, Gómez SY, Cortés FM, , 2015. Dengue hemorrhagic fever serotype and infection pattern in a Colombian endemic area. Rev Salud Pública (Bogota) 9: 262274. [Google Scholar]
  61. Jones JM, 2016. Binational dengue outbreak along the United States-Mexico border - Yuma County, Arizona, and Sonora, Mexico, 2014. MMWR Morb Mortal Wkly Rep 65: 495499. [Google Scholar]
  62. Luo L, Liang HY, Hu YS, Liu WJ, Wang YL, Jing QL, Zheng XL, Yang ZC, , 2012. Epidemiological, virological, and entomological characteristics of dengue from 1978 to 2009 in Guangzhou, China. J Vector Ecol 37: 230240. [Google Scholar]
  63. Shi Y, Li S, Li X, Zheng K, Yuan S, Huang J, , 2016. Epidemiological and molecular characterization of dengue viruses imported into Guangzhou during 2009–2013. Springerplus 5: 1635. [Google Scholar]
  64. Sun J, Wu D, Zhou H, Zhang H, Guan D, He X, Cai S, Ke C, Lin J, , 2016. The epidemiological characteristics and genetic diversity of dengue virus during the third largest historical outbreak of dengue in Guangdong, China, in 2014. J Infect 72: 8090. [Google Scholar]
  65. Yanbo L, , 2003. Prediction of the secondary structure and B cell epitopes for the M protein of SARS coronavirus. Prog Biotechnol 23: 4145. [Google Scholar]
  66. Wood MJ, Hirst JD, , 2005. Protein secondary structure prediction with dihedral angles. Proteins 59: 476481. [Google Scholar]
  67. Zhao W, Cao H, Yang F, Xie Q, Zhang B, Yu J, Wu Q, , 2017. Structure and function of the non-structural protein of dengue virus and its applications in antiviral therapy. Curr Top Med Chem 17: 110. [Google Scholar]
  68. Moraes AH, Simonelli L, Pedotti M, Almeida FC, Varani L, Valente AP, , 2016. Antibody binding modulates conformational exchange in domain III of dengue virus E protein. J Virol 90: 18021811. [Google Scholar]
  69. Nayak V, Dessau M, Kucera K, Anthony K, Ledizet M, Modis Y, . 2009. Crystal structure of dengue virus type 1 envelope protein in the postfusion conformation and its implications for membrane fusion. J Food Prot 83: 662667. [Google Scholar]
  70. Drumond BP, 2016. Phylogenetic analysis of dengue virus 1 isolated from south Minas Gerais, Brazil. Braz J Microbiol 47: 251258. [Google Scholar]
  71. Wadood A, Mehmood A, Khan H, Ilyas M, Ahmad A, Alarjah M, Abu-Izneid T, , 2017. Epitopes based drug design for dengue virus envelope protein: a computational approach. Comput Biol Chem 71: 152160. [Google Scholar]
  72. Chen WH, Chou FP, Wang YK, Huang SC, Cheng CH, Wu TK, , 2017. Characterization and epitope mapping of dengue virus type 1 specific monoclonal antibodies. Virol J 14: 189. [Google Scholar]

Data & Media loading...

  • Received : 29 Nov 2018
  • Accepted : 26 Jun 2019
  • Published online : 05 Aug 2019

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