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Selection-driven evolution of emergent dengue virus.

Shannon N Bennett1, Edward C Holmes, Maritza Chirivella

  • 1Department of Biology, University of Puerto Rico-Rio Piedras, San Juan, Puerto Rico, USA. sbennett@rrpac.upr.clu.edu

Molecular Biology and Evolution
|July 2, 2003
PubMed
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Dengue fever incidence has surged globally. This study reveals that changes in the dengue virus type 4 (DEN-4) nonstructural gene 2A (NS2A) significantly influenced viral evolution and epidemic expansion in Puerto Rico.

Area of Science:

  • Virology
  • Molecular Evolution
  • Epidemiology

Background:

  • Dengue fever incidence has increased 30-fold globally in the last four decades.
  • Over half the world's population is at risk from four dengue virus serotypes (DEN-1 to DEN-4).

Purpose of the Study:

  • To investigate the role of viral molecular evolution in the dynamics of emergent dengue disease.
  • To analyze evolutionary shifts in dengue virus type 4 (DEN-4) populations in Puerto Rico over a 20-year period.

Main Methods:

  • Sequencing of 40% of the genome from 82 DEN-4 isolates collected in Puerto Rico over 20 years.
  • Analysis of viral lineage turnover and genetic changes in relation to epidemic prevalence.
  • Examination of positive selection pressures on viral genes, particularly nonstructural gene 2A (NS2A).

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Main Results:

  • Marked evolutionary shifts and temporal clustering of DEN-4 viral lineages were observed in Puerto Rico.
  • Changes in structural genes did not appear to drive lineage turnover.
  • Positive selection on the NS2A gene was identified as a key factor in recent dengue evolution and epidemic expansion.
  • Three specific amino acid changes in NS2A were rapidly fixed during the 1998 DEN-4 epidemic, exceeding expected rates of genetic drift.

Conclusions:

  • Viral genetic turnover occurs within focal populations.
  • Adaptive evolution, particularly driven by changes in the NS2A gene, plays a significant role in viral epidemic expansion.
  • Understanding viral molecular evolution is crucial for managing emergent infectious diseases like dengue fever.