Molecular evolution and epidemiology of four serotypes of dengue virus in Thailand from 1973 to 2007

Abstract

Thailand was a hyper-endemic country for dengue with co-circulation of four serotypes and tens of thousands of infected cases annually. Taking into consideration the large number of local dengue virus (DENV) sequences available in GenBank, Thailand was the most ideal locality to study co-evolution of DENV. Therefore, we undertook a large-scale molecular epidemiological analysis of all DENV strains isolated in Thailand. In this study, we demonstrated that DENV strains of four serotypes post-1990 grouped into distinct clades, and that specific mutations in the envelope protein were first confirmed in these clades. Compared to the DENV1, DENV2 and DENV3 clades, the DENV4 clade evolved markedly more slowly (6·4 × 10-5 substitutions/site per year). Our results also showed that the genetic diversity of the predominant genotype of each serotype tended to slightly increase over time with fluctuating changes, followed by a stationary phase after 2000. This suggests that the four DENV clades became the predominant strains due to DENV possessing improved fitness after long-term selection.

Plaque reduction neutralization antibody test does not accurately predict protection against dengue infection in Ratchaburi cohort, Thailand

“…Finally, the pre-infection PRNT50 titers are against reference dengue-virus strains. As molecular evolution among dengue viruses has been continuous [ 21 ], it may cause antigenic mismatches between the reference dengue virus strains used in the PRNT and infecting viruses, and therefore, mismatch between the pre-existing antibody and the antigen of the infecting homologous serotype. Further studies are needed to clarify these possibilities.…”

Understanding dengue virus evolution to support epidemic surveillance and counter-measure development

“…This raised the prospect of using viral phylodynamic signal as an early signal for subsequent DENV epidemic peaks and also validated the thoroughness of conventional surveillance methods based on case/lab-positive counts alone. This study was particularly robust as it coupled serial case count data alongside estimates of DENV-4 diversity before making conclusions, a critical practice to ensure that changes in genetic diversity truly represent the circulating viral population and not merely variability in sampling adequacy, which has been a limitation in interpreting Skyline plots in other studies [145,165,166]. Longitudinal diversity plots can also reconstruct the R 0 of specific DENV epidemics (albeit with limitations such as requiring prior knowledge of the sampling strategy) and examine the impact of public health interventions such as vector control on the effective DENV population size, complementing non-genomic modeling approaches [163,167].…”

Developing a dengue vaccine: progress and future challenges

“…This was a leading hypothesis for CYD's phase IIb performance (DENV‐2 efficacy ∼9%), but currently available data would not support this conclusion. Regardless, there is an extensive and growing body of data describing DENV epidemiologic trends and the potential that variations in circulating genotypes may influence observed clinical phenotypes . There are indications that only a few strategically placed mutations in the DENV genome may be necessary to have significant impacts on its ability to be neutralized .…”

“…Regardless, there is an extensive and growing body of data describing DENV epidemiologic trends and the potential that variations in circulating genotypes may influence observed clinical phenotypes. [186][187][188][189][190] There are indications that only a few strategically placed mutations in the DENV genome may be necessary to have significant impacts on its ability to be neutralized. 191 The most significant implication would be the recurring requirement for developers to update their licensed vaccines with contemporary DENV strains (e.g., similar to influenza but with a more protracted timeline).…”