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Journal of Virology, May 2009, p. 4163-4173, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02445-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Genomic Epidemiology of a Dengue Virus Epidemic in Urban Singapore{triangledown} ,{dagger}

Mark J. Schreiber,1* Edward C. Holmes,2,3 Swee Hoe Ong,1,4,5 Harold S. H. Soh,6 Wei Liu,1 Lukas Tanner,1 Pauline P. K. Aw,4 Hwee Cheng Tan,7 Lee Ching Ng,7 Yee Sin Leo,8 Jenny G. H. Low,8 Adrian Ong,8 Eng Eong Ooi,9 Subhash G. Vasudevan,1,{ddagger} and Martin L. Hibberd4

Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos 05-01, Singapore 138670,1 Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802,2 Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892,3 Genome Institute of Singapore, A*STAR, 60 Biopolis Street, Genome 02-01, Singapore 138672,4 Swiss Tropical Institute, Socinstrasse 57, P.O. Box CH-4002, Basel, Switzerland,5 Institute for High Performance Computing, A*STAR, 1 Science Park Road, 01-01 The Capricorn, Singapore Science Park II, Singapore 117528,6 National Environment Agency, 40 Scotts Road, 13-00, Singapore 228231,7 Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433,8 DSO National Laboratories, 27 Medical Drive, 09-01, Singapore 1175109

Received 26 November 2008/ Accepted 3 February 2009

Dengue is one of the most important emerging diseases of humans, with no preventative vaccines or antiviral cures available at present. Although one-third of the world's population live at risk of infection, little is known about the pattern and dynamics of dengue virus (DENV) within outbreak situations. By exploiting genomic data from an intensively studied major outbreak, we are able to describe the molecular epidemiology of DENV at a uniquely fine-scaled temporal and spatial resolution. Two DENV serotypes (DENV-1 and DENV-3), and multiple component genotypes, spread concurrently and with similar epidemiological and evolutionary profiles during the initial outbreak phase of a major dengue epidemic that took place in Singapore during 2005. Although DENV-1 and DENV-3 differed in viremia and clinical outcome, there was no evidence for adaptive evolution before, during, or after the outbreak, indicating that ecological or immunological rather than virological factors were the key determinants of epidemic dynamics.

* Corresponding author. Mailing address: Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos 05-01, Singapore 138670. Phone: (65) 672-2973. Fax: (65) 672-2910. E-mail: mark.schreiber{at}novartis.com

{triangledown} Published ahead of print on 11 February 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, 2 Jalan Bukit Merah, Singapore 169547.

Journal of Virology, May 2009, p. 4163-4173, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02445-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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