Abstract
Dengue has been well recognized as a global public health threat, but only sporadic epidemics and imported cases were reported in recent decades in China. Since July 2014, an unexpected large dengue outbreak has occurred in Guangdong province, China, resulting in more than 40000 patients including six deaths. To clarify and characterize the causative agent of this outbreak, the acute phase serum from a patient diagnosed with severe dengue was subjected to virus isolation and high-throughput sequencing (HTS). Traditional real-time RT-PCR and HTS with Ion Torrent PGM detected the presence of dengue virus serotype 2 (DENV-2). A clinical DENV-2 isolate GZ05/2014 was obtained by culturing the patient serum in mosquito C6/36 cells. The complete genome of GZ05/2014 was determined and deposited in GenBank under the access number KP012546. Phylogenetic analysis based on the complete envelope gene showed that the newly DENV-2 isolate belonged to Cosmopolitan genotype and clustered closely with other Guangdong strains isolated in the past decade. No amino acid mutations that are obviously known to increase virulence or replication were identified throughout the genome of GZ05/2014. The high homology of Guangdong DENV-2 strains indicated the possibility of establishment of local DENV-2 circulation in Guangdong, China. These results help clarify the origin of this epidemic and predict the future status of dengue in China.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI. The global distribution and burden of dengue. Nature, 2013, 496: 504–507
Elling R, Henneke P, Hatz C, Hufnagel M. Dengue fever in children: where are we now? Pediatr Infect Dis J, 2013, 32: 1020–1022
Morens DM. Antibody-dependent enhancement of infection and the pathogenesis of viral disease. Clin Infect Dis, 1994, 19: 500–512
WHO/ TDR. Dengue—Guidelines for diagnosis, treatment, prevention and control. 2009, http://www.who.int/tdr/publications/training-guideline-publications/dengue-diagnosis-treatment/en/index.html
Wu JY, Lun ZR, James AA, Chen XG. Dengue Fever in mainland China. Am J Tropical Med Hygiene, 2010, 83: 664–671
Li TG, Yang ZC, Luo L, Di B, Wang M. Dengue Fever epidemiological status and relationship with meteorological variables in Guangzhou, Southern China, 2007–2012. Biomed Environ Sci, 2013, 26: 994–997
Jiang L, Wu X, Wu Y, Bai Z, Jing Q, Luo L, Dong Z, Yang Z, Xu Y, Cao Y, Di B, Wang Y, Wang M. Molecular epidemiological and virological study of dengue virus infections in Guangzhou, China, during 2001–2010. Virol J, 2013, 10: 4
Wu LQ, Zhang XM, Che YC, Zhang Y, Tang SQ, Liao Y, Na RX, Xiong XL, Liu LD, Li QH. A cellular response protein induced during HSV-1 infection inhibits viral replication by interacting with ATF5. Sci China Life Sci, 2013, 56: 1124–1133
Yang EX, Zhao H, Zhang Y, Liu JS, Liao Y, Wang LC, Cui PF, Yang LX, Liu LD, Dong CH, Dong SZ, Shao CW, Jiang L, Sun L, Li QH. A comparative study of the characteristics of two Coxsackie A virus type 16 strains (genotype B). Sci China Life Sci, 2012, 55: 336–342
Deng YQ, Dai JX, Ji GH, Jiang T, Wang HJ, Yang HO, Tan WL, Liu R, Yu M, Ge BX, Zhu QY, Qin ED, Guo YJ, Qin CF. A broadly flavivirus cross-neutralizing monoclonal antibody that recognizes a novel epitope within the fusion loop of E protein. PLoS One, 2011, 6: e16059
Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG. Clustal W and Clustal X version 2.0. Bioinformatics, 2007, 23: 2947–2948
Geng H, Tan W. A novel human coronavirus: middle East respiratory syndrome human coronavirus. Sci China Life Sci, 2013, 56: 683–687
Bryant JE, Calvert AE, Mesesan K, Crabtree MB, Volpe KE, Silengo S, Kinney RM, Huang CY, Miller BR, Roehrig JT. Glycosylation of the dengue 2 virus E protein at N67 is critical for virus growth in vitro but not for growth in intrathoracically inoculated Aedes aegypti mosquitoes. Virology, 2007, 366: 415–423
Bray M, Men R, Tokimatsu I, Lai CJ. Genetic determinants responsible for acquisition of dengue type 2 virus mouse neurovirulence. J Virol, 1998, 72: 1647–1651
Butrapet S, Childers T, Moss KJ, Erb SM, Luy BE, Calvert AE, Blair CD, Roehrig JT, Huang CY. Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion. Virology, 2011, 413: 118–127
Prestwood TR, Prigozhin DM, Sharar KL, Zellweger RM, Shresta S. A mouse-passaged dengue virus strain with reduced affinity for heparan sulfate causes severe disease in mice by establishing increased systemic viral loads. J Virol, 2008, 82: 8411–8421
Sanchez IJ, Ruiz BH. A single nucleotide change in the E protein gene of dengue virus 2 Mexican strain affects neurovirulence in mice. J Gen Virol, 1996, 77 (Pt 10): 2541–2545
Huang CY, Butrapet S, Moss KJ, Childers T, Erb SM, Calvert AE, Silengo SJ, Kinney RM, Blair CD, Roehrig JT. The dengue virus type 2 envelope protein fusion peptide is essential for membrane fusion. Virology, 2010, 396: 305–315
Lin SR, Zou G, Hsieh SC, Qing M, Tsai WY, Shi PY, Wang WK. The helical domains of the stem region of dengue virus envelope protein are involved in both virus assembly and entry. J Virol, 2011, 85: 5159–5171
OhAinle M, Balmaseda A, Macalalad AR, Tellez Y, Zody MC, Saborio S, Nunez A, Lennon NJ, Birren BW, Gordon A, Henn MR, Harris E. Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity. Sci Trans Med, 2011, 3: 114ra128
Butrapet S, Huang CY, Pierro DJ, Bhamarapravati N, Gubler DJ, Kinney RM. Attenuation markers of a candidate dengue type 2 vaccine virus, strain 16681 (PDK-53), are defined by mutations in the 5′ noncoding region and nonstructural proteins 1 and 3. J Virol, 2000, 74: 3011–3019
Grant D, Tan GK, Qing M, Ng JK, Yip A, Zou G, Xie X, Yuan Z, Schreiber MJ, Schul W, Shi PY, Alonso S. A single amino acid in nonstructural protein NS4B confers virulence to dengue virus in AG129 mice through enhancement of viral RNA synthesis. J Virol, 2011, 85: 7775–7787
Zhao W, Fan B, Hu Z, Chen S, Wang P, Yuan X, Li X, Yu M, Qin E, Yang P. Study on the determinants of suckling mice neurovirulence of dengue 2 virus. Sci China Ser C-Life Sci, 2003, 46: 95–103
Quiner CA, Parameswaran P, Ciota AT, Ehrbar DJ, Dodson BL, Schlesinger S, Kramer LD, Harris E. Increased replicative fitness of a dengue virus 2 clade in native mosquitoes: potential contribution to a clade replacement event in Nicaragua. J Virol, 2014, 88: 13125–13134
Wu W, Bai Z, Zhou H, Tu Z, Fang M, Tang B, Liu J, Liu L, Liu J, Chen W. Molecular epidemiology of dengue viruses in southern China from 1978 to 2006. Virol J, 2011, 8: 322
Zhang FC, Zhao H, Li LH, Jiang T, Hong WX, Wang J, Zhao LZ, Yang HQ, Ma DH, Bai CH, Shan XY, Deng YQ, Qin CF. Severe dengue outbreak in Yunnan, China, 2013. Int J Infect Dis, 2014, 27: 4–6
Zhao H, Yu XD, Zhang XY, Jiang T, Hong WX, Yu M, Hu FY, Zhu SY, Qin ED, Deng YQ, Qin CF, Zhang FC. Complete genome sequence of a dengue virus serotype 4 strain isolated in Guangdong, China. J Virol, 2012, 86: 7021–7022
Zhao H, Deng YQ, Hong WX, Yu XD, Jiang T, Yu M, Hu FY, Zhu SY, Li XF, Song KY, Qin ED, Zhang FC, Qin CF. Complete genome sequence of dengue virus serotype 2 Cosmopolitan genotype strain in Guangdong, China. J Virol, 2012, 86: 13808–13809
Jing QL, Yang ZC, Luo L, Xiao XC, Di B, He P, Fu CX, Wang M, Lu JH. Emergence of dengue virus 4 genotype II in Guangzhou, China, 2010: survey and molecular epidemiology of one community outbreak. BMC Infect Dis, 2012, 12: 87
Jiang T, Yu XD, Hong WX, Zhou WZ, Yu M, Deng YQ, Zhu SY, Qin ED, Wang J, Qin CF, Zhang FC. Co-circulation of two genotypes of dengue virus serotype 3 in Guangzhou, China, 2009. Virol J, 2012, 9: 125
Hong WX, Zhao H, Deng YQ, Jiang T, Yu XD, Song KY, Wang J, Tan XH, Yu M, Zhu SY, Qin ED, Tang XP, Zhang FC, Qin CF. Severe dengue due to secondary DENV-1 infection in mainland China. J Clin Virol, 2013, 57: 184–186
Author information
Authors and Affiliations
Corresponding authors
Additional information
Contributed equally to this work
This article is published with open access at springerlink.fh-diploma.de
Electronic supplementary material
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Zhao, H., Zhao, L., Jiang, T. et al. Isolation and characterization of dengue virus serotype 2 from the large dengue outbreak in Guangdong, China in 2014. Sci. China Life Sci. 57, 1149–1155 (2014). https://doi.org/10.1007/s11427-014-4782-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-014-4782-3