The RNA secondary structural variation in the cyclization elements of the dengue genome and the possible implications in
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ORIGINAL ARTICLE
The RNA secondary structural variation in the cyclization elements of the dengue genome and the possible implications in pathogenicity Bibhudutta Mishra1 • Advait Balaji1 • Hemalatha Beesetti2,3 • Sathyamangalam Swaminathan2,3 • Raviprasad Aduri1
Received: 15 April 2020 / Accepted: 20 July 2020 Indian Virological Society 2020
Abstract 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 50 and 30 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 50 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.
Advait Balaji and Hemalatha Beesetti have contributed equally.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13337-020-00615-w) contains supplementary material, which is available to authorized users. & Raviprasad Aduri [email protected] 1
Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, K K Birla Goa Campus, Zuarinagar, South Goa, Goa 403 726, India
2
Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, Hyderabad, Telangana 500 078, India
3
Present Address: Molecular Medicine Division, Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India
Keywords Dengue virus Serotypes Genotypes RNA secondary structure Pathogenicity UTRs
Introduction Dengue virus (DENV) belonging to family Flaviviridae causes illness ranging from dengue fever (DF) to more severe dengue (DHF and DSS). Recent estimates suggest the occurrence of 390 million new dengue infections per year with 3.9 billion people being at risk [8]. Dengue exists as four antigenically different serotypes, DENV 1–4. Though each of the serotypes is known to cause symptomatic disease in humans [21, 31], DENV 2 infections are more often associated with severe dengue followed by DENV 3 infections [7, 19, 32–34, 40]. Each of the four serotypes is further classified into different genotypes, reportedly having varying degrees of pathogenicity [22]. The presence of genetic variation within a serotype has been attributed to differences in viral fitness, pathogenicity, and ability to cause epidemics [14, 25, 34, 43]. For example, Rico-Hesse’s group has shown that the introduction of
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