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Journal of Virology, June 2008, p. 5494-5500, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02728-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Microevolution of Dengue Viruses Circulating among Primary School Children in Kamphaeng Phet, Thailand{triangledown}

Richard G. Jarman,1* Edward C. Holmes,2,3 Prinyada Rodpradit,1 Chonticha Klungthong,1 Robert V. Gibbons,1 Ananda Nisalak,1 Alan L. Rothman,4 Daniel H. Libraty,4 Francis A. Ennis,4 Mammen P. Mammen Jr.,1 and Timothy P. Endy5

Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok, Thailand 10400,1 Center for Infectious Disease Dynamics, Department of Biology, Mueller Laboratory, The Pennsylvania State University, University Park, Pennsylvania 16802,2 Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892,3 Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655,4 State University of New York Upstate Medical University, Syracuse, New York 132105

Received 22 December 2007/ Accepted 28 February 2008

To determine the extent and structure of genetic variation in dengue viruses (DENV) on a restricted spatial and temporal scale, we sequenced the E (envelope) genes of DENV-1, -2, and -3 isolates collected in 2001 from children enrolled in a prospective school-based study in Kamphaeng Phet, Thailand, and diagnosed with dengue disease. Our analysis revealed substantial viral genetic variation in both time and space, with multiple viral lineages circulating within individual schools, suggesting the frequent gene flow of DENV into this microenvironment. More-detailed analyses of DENV-2 samples revealed strong clustering of viral isolates within individual schools and evidence of more-frequent viral gene flow among schools closely related in space. Conversely, we observed little evolutionary change in those viral isolates sampled over multiple time points within individual schools, indicating a low rate of mutation fixation. These results suggest that frequent viral migration into Kamphaeng Phet, coupled with population (school) subdivision, shapes the genetic diversity of DENV on a local scale, more so than in situ evolution within school catchment areas.

* Corresponding author. Mailing address: Department of Virology, USAMC-AFRIMS, APO, AP 96546, 315/6 Rajvithi Road, Bangkok, Thailand 10400. Phone: (662) 644-5644. Fax: (662) 644-4760. E-mail: Richard.Jarman{at}afrims.org

{triangledown} Published ahead of print on 26 March 2008.

Journal of Virology, June 2008, p. 5494-5500, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02728-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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