The RNA Secondary Structural Variation in the Cyclization Elements of the Dengue Genome and the Possible Implications in Pathogenicity

Dengue virus (DENV), the causative agent of dengue fever and severe dengue, exists as four antigenically different serotypes. These serotypes are further classified into genotypes and have varying degrees of pathogenicity. The 5' and 3' ends of the genomic RNA play a critical role in the viral life cycle. A global scale study of the RNA structural variation among the sero- and genotypes was carried out to correlate RNA structure with pathogenicity. We found that the GC rich stem and rigid loop structure of the 5' end of the genomic RNA of DENV 2 differs significantly from the others. The observed variation in base composition and base pairing may confer structural and functional advantage in highly virulent strains. This variation in the structure may influence the ease of cyclization and recruitment of viral RNA polymerase, NS5 RdRp, thereby affecting the pathogenicity of these strains.