Genetic Variation in the Domain II, 3′ Untranslated Region of Human and Mosquito Derived Dengue Virus Strains in Sri Lanka

Abstract

Genetic variations in dengue virus (DENV) play a distinct role in epidemic emergence. The DENV 3′ UTR has become a recent interest in research. The objective of the study was to examine the genetic variation in the domain II, 3′ UTR region of human and mosquito-derived DENV. DENV-infected human sera were orally infected to laboratory reared Aedes aegypti mosquitoes. The domain II, 3′ UTR of each human- and mosquito-derived sample was amplified. The nucleotide sequence variation, phylogenetic and secondary structure analysis was carried out incorporating respective regions of so far recorded Sri Lankan and the reference genotype strains of the DENV3 and DENV1 serotypes. The human- and mosquito-derived domain II, 3′ UTR were identical in nucleotide sequences within the serotypes isolated, indicating the conserved nature of the region during host switch. The sequence analysis revealed distinct variations in study isolates compared to so far recorded Sri Lankan isolates. However, despite single nucleotide variations, the maintenance of structural integrity was evident in related strains within the serotypes in the secondary structure analysis. The phylogenetic analysis revealed distinct clade segregation of the study sequences from so far reported Sri Lankan isolates and illustrated the phylogenetic relations of the study sequences to the available global isolates of respective serotypes.

Association of Dengue Virus Serotypes 1&2 with Severe Dengue Having Deletions in Their 3′Untranslated Regions (3′UTRs)

“…The possibility of increased transmission and epidemic situations has been reported if any minor genetic changes occur in flavivirus RNA [ 26 ]. Furthermore, it has been reported that genetic variation in 3′UTR contributes to epidemic emergence [ 27 ]. Several reports have suggested that the insertions/deletions in 3′UTR have recently contributed to disease pathogenicity [ 4 ].…”

Interactions of host miRNAs in the flavivirus 3´UTR genome: From bioinformatics predictions to practical approaches

“…This basic structure is also observed in JEV, WNV, MVE and KUN. The DB2 structure is absent in YFV and ZIKV, and both DB1 and DB2 are absent in the TBE genome; however, the formation of pseudoknots is apparently a common feature observed in all MBFV ( Olsthoorn and Bol, 2001 ; Funk et al., 2010 ; Kasprzak and Shapiro, 2014 ; de Borba et al., 2019 ; Dayananda et al., 2021 ). These structures are relevant for replication efficiency, since mutations that disrupt them result in the generation of DENV-3 with an attenuated phenotype in SCID-Huh-7 mice, mosquitoes, and rhesus monkeys ( Blaney et al., 2008 ; de Borba et al., 2019 ) and a reduction in the replication efficiency of KUN ( Funk et al., 2010 ).…”