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

Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok, Thailand 10400.
Journal of Virology (Impact Factor: 4.44). 07/2008; 82(11):5494-500. DOI: 10.1128/JVI.02728-07
Source: PubMed


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.

Download full-text


Available from: Mammen P Mammen, Nov 03, 2014
21 Reads
  • Source
    • "Previous work did not detect significant differences in EIP between DENV serotypes [11] and wide-scale differences in competence between different strains of Ae. aegypti are difficult to demonstrate considering the degree of variability in vector competence studies (Figure 1). Although there is some evidence of fine scale variation in competence in both mosquito [78-80] and virus [81,82] populations, more research is needed to determine if such structure exists at a wider scale considering human assisted rapid movement of vector and viruses may minimise opportunities for evolutionary interactions [83,84]. Until wider spatial scale structuring of mosquito-virus interaction can be demonstrated, a generalised prediction using vector and virus strains from a variety of different conditions is most likely to be representative of the majority of transmission environments. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Dengue is a disease that has undergone significant expansion over the past hundred years. Understanding what factors limit the distribution of transmission can be used to predict current and future limits to further dengue expansion. While not the only factor, temperature plays an important role in defining these limits. Previous attempts to analyse the effect of temperature on the geographic distribution of dengue have not considered its dynamic intra-annual and diurnal change and its cumulative effects on mosquito and virus populations. Methods Here we expand an existing modelling framework with new temperature-based relationships to model an index proportional to the basic reproductive number of the dengue virus. This model framework is combined with high spatial and temporal resolution global temperature data to model the effects of temperature on Aedes aegypti and Ae. albopictus persistence and competence for dengue virus transmission. Results Our model predicted areas where temperature is not expected to permit transmission and/or Aedes persistence throughout the year. By reanalysing existing experimental data our analysis indicates that Ae. albopictus, often considered a minor vector of dengue, has comparable rates of virus dissemination to its primary vector, Ae. aegypti, and when the longer lifespan of Ae. albopictus is considered its competence for dengue virus transmission far exceeds that of Ae. aegypti. Conclusions These results can be used to analyse the effects of temperature and other contributing factors on the expansion of dengue or its Aedes vectors. Our finding that Ae. albopictus has a greater capacity for dengue transmission than Ae. aegypti is contrary to current explanations for the comparative rarity of dengue transmission in established Ae. albopictus populations. This suggests that the limited capacity of Ae. albopictus to transmit DENV is more dependent on its ecology than vector competence. The recommendations, which we explicitly outlined here, point to clear targets for entomological investigation.
    Parasites & Vectors 07/2014; 7(1):338. DOI:10.1186/1756-3305-7-338 · 3.43 Impact Factor
  • Source
    • "Dengue evolution has been characterized by vigorous purifying selection (Holmes 2003, Twiddy et al. J Gen Virol 2002), occasional positive selection on certain amino acid sites (Bennett et al. 2003, Bennett et al. 2006, Twiddy Virology 2002) and considerable genetic drift (Jarman et al. 2008), particularly important in small populations. Genetic drift might be expected to predominate as a force of evolutionary change in the South Pacific simply because islands experience relatively more population bottlenecks, that is, drastic reductions of individuals leading to random fixation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dengue is an expanding arboviral disease of variable severity characterized by the emergence of virus strains with greater fitness, epidemic potential and possibly virulence. To investigate the role of dengue virus (DENV) strain variation on epidemic activity we studied DENV-2 viruses from a series of South Pacific islands experiencing outbreaks of varying intensity and clinical severity. Initially appearing in 1971 in Tahiti and Fiji, the virus was responsible for subsequent epidemics in American Samoa, New Caledonia and Niue Island in 1972, reaching Tonga in 1973 where there was near-silent transmission for over a year. Based on whole-genome sequencing and phylogenetic analysis on 20 virus isolates, Tonga viruses were genetically unique, clustering in a single clade. Substitutions in the pre-membrane (prM) and nonstructural genes NS2A and NS4A correlated with the attenuation of the Tongan viruses and suggest that genetic change may play a significant role in dengue epidemic severity.
    Virology 09/2010; 405(2):505-12. DOI:10.1016/j.virol.2010.05.033 · 3.32 Impact Factor
  • Source
    • "Indeed, G × G interactions indicate that elimination of viruses that are incompatible with local mosquito genotypes may counteract the effect of genetic drift in the form of purifying selection at the population level. Likewise, the observed spatial clustering of DENV lineages on a restricted spatial scale [8] may in fact be promoted by location-specific vector-driven selection. Over time, genetic specificity of vector-virus compatibility would combine with the genetic structure of Ae. aegypti populations to drive the adaptation of DENV to increased compatibility with local mosquito genotypes [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Several observations support the hypothesis that vector-driven selection plays an important role in shaping dengue virus (DENV) genetic diversity. Clustering of DENV genetic diversity at a particular location may reflect underlying genetic structure of vector populations, which combined with specific vector genotype x virus genotype (G x G) interactions may promote adaptation of viral lineages to local mosquito vector genotypes. Although spatial structure of vector polymorphism at neutral genetic loci is well-documented, existence of G x G interactions between mosquito and virus genotypes has not been formally demonstrated in natural populations. Here we measure G x G interactions in a system representative of a natural situation in Thailand by challenging three isofemale families from field-derived Aedes aegypti with three contemporaneous low-passage isolates of DENV-1. Among indices of vector competence examined, the proportion of mosquitoes with a midgut infection, viral RNA concentration in the body, and quantity of virus disseminated to the head/legs (but not the proportion of infected mosquitoes with a disseminated infection) strongly depended on the specific combinations of isofemale families and viral isolates, demonstrating significant G x G interactions. Evidence for genetic specificity of interactions in our simple experimental design indicates that vector competence of Ae. aegypti for DENV is likely governed to a large extent by G x G interactions in genetically diverse, natural populations. This result challenges the general relevance of conclusions from laboratory systems that consist of a single combination of mosquito and DENV genotypes. Combined with earlier evidence for fine-scale genetic structure of natural Ae. aegypti populations, our finding indicates that the necessary conditions for local DENV adaptation to mosquito vectors are met.
    BMC Evolutionary Biology 02/2009; 9(1):160. DOI:10.1186/1471-2148-9-160 · 3.37 Impact Factor
Show more