JVI Accepts, published online ahead of print on 26 March 2008

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J. Virol. doi:10.1128/JVI.02728-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Microevolution of Dengue Viruses Circulating Among Primary School Children in Kamphaeng Phet, Thailand

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

Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok, Thailand 10400; Center for Infectious Disease Dynamics, Department of Biology, Mueller Laboratory, The Pennsylvania State University, University Park, PA 16802. USA; Fogarty International Center, National Institutes of Health, Bethesda, MD 20892. USA; Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA; University of New York, Upstate Medical University, Syracuse, NY 13210. USA

^* To whom correspondence should be addressed. Email: Richard.Jarman{at}afrims.org.

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) gene of DENV-1, 2, and 3 isolated from children with confirmed dengue disease in 2001 enrolled in a prospective school-based study in Kamphaeng Phet, Thailand. 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 a 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 a combination of frequent viral migration into Kamphaeng Phet coupled with population (school) subdivision, more so than in situ evolution within school catchment areas, shapes the genetic diversity of DENV at a local scale.

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