Genetic analysis of Dengue 3 virus subtype III 5' and 3' non-coding regions

Area of Science:

• Virology
• Molecular Epidemiology
• Genetics

Background:

• Dengue hemorrhagic fever emerged in Sri Lanka in 1989, coinciding with a new Dengue 3 virus (DENV-3) subtype III variant (group B).
• This variant is genetically similar to the endemic group A variant.
• Understanding DENV-3 genetic diversity is crucial for disease control.

Purpose of the Study:

• To investigate the genetic variability within the 5' and 3' non-coding regions (NCRs) of DENV-3 subtype III isolates.
• To correlate genetic differences with geographic origin and disease severity.
• To assess the utility of the 3' NCR for molecular epidemiology of DENV-3.

Main Methods:

• Sequencing of the 5' and 3' non-coding regions (NCRs) of 15 DENV-3 subtype III isolates from Sri Lanka, Nicaragua, and Martinique.
• Phylogenetic analysis to determine viral relationships and origins.
• Comparative analysis of nucleotide sequences to identify genetic variations.

Main Results:

• Variability was observed in the 3' NCRs, including an 11-nucleotide insertion common to all studied isolates.
• Two nucleotide differences geographically segregated isolates into American and Sri Lankan groups.
• Three nucleotide differences distinguished mild (group A) from severe (group B) DENV-3 epidemics, with group B isolates clustering with Latin American/Caribbean strains.

Conclusions:

• The 3' NCR is a valuable marker for molecular epidemiologic studies of DENV-3.
• Geographic clustering and genetic differences in the 3' NCR support a common East African origin for these DENV-3 strains.
• Observed genetic variations in the 3' NCR and coding regions may contribute to the increased pathogenicity of group B DENV-3.