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Evolution of Dengue Virus Type 2 during Two Consecutive Outbreaks with an Increase in Severity in Southern Taiwan in 2001–2002

To investigate viral determinants and evolution linked to outbreak with increased severity, we examined dengue virus type 2 (DENV-2) sequences from plasma of 31 patients (14 dengue fever, 17 dengue hemorrhagic fever, DHF) continuously during the 2001 and 2002 outbreaks in southern Taiwan, in which both the total cases and proportion of DHF cases increased. Analysis of envelope (E) and full-genome sequences between viruses of the two outbreaks revealed 5 nucleotide changes in E, NS1, NS4A, and NS5 genes. None was identical to those reported in the DENV-2 outbreak in Cuba in 1997, suggesting viral determinants linked to severe outbreak are genotype dependent. Compared with previous reports of lineage turnover years apart, our findings that the 2002 viruses descended from a minor variant of the 2001 viruses in less than 6 months was novel, and may represent a mechanism of evolution of DENV from one outbreak to another.

Received September 19, 2007. Accepted for publication June 14, 2008.

Acknowledgments: We thank Dr. Chung-Chou Juan and Shu-Mei Chang at the Yuan’s General Hospital, Dr. Cheng-Ching Yu and Li-Hui Lin at the Hui-Te Hospital in the Kaohsiung area for kindly providing clinical samples, Dr. Jyh-Hsiung Huang at the Center for Disease Control, Department of Health Taiwan for the information on primary and secondary infection, Mien-Huei Wu, Chao-Fu Yang, Mei-Ying Liao, I-Jung Liu, and Hsien-Ping Hu for technical assistance.

Financial support: This work was supported by the National Science Council (NSC95-2320-B-002-084-MY3), Taiwan.

^* Address correspondence to Wei-Kung Wang, Institute of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd, Taipei, Taiwan. E-mail: wwang60{at}yahoo.com

Authors’ addresses: Hui-Ling Chen, Su-Ru Lin, Szu-Chia Hsieh, and Wei-Kung Wang, Institute of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd, Taipei, Taiwan, Tel: 8862-2312-3456 ext. 8286, Fax: 8862-2391-5293, E-mail: wwang60{at}yahoo.com. Hsin-Fu Liu, Department of Medical Research, Mackay Memorial Hospital, 45 Min-Sheng Rd, c-Tamshui, Taiwan, Tel: 8862-2809-4661 ext. 2073. Chwan-Chuen King, Institute of Epidemiology, College of Public Health, National Taiwan University, No. 17, Hsu-Chou Rd, Taipei, Taiwan, Tel: 8862-2341-4347.

Note: The sequences have been submitted to Genbank (Table 1). Supplemental Tables 1–3 appear online at www.ajtmh.org.

Reprint requests: Wei-Kung Wang, Institute of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd, Taipei, Taiwan, Tel: 8862-2312-3456 ext. 8286, Fax: 8862-2391-5293, E-mail: wwang60{at}yahoo.com.