**5.3 Untranslated Region (UTR) mutations**

The 3' UTR region is thought to play a pivotal role in the DENV biology; it contains several conserved regions as well as 3' long Stable Hair Pin structure which is conserved among all the members of the family *Flaviviridae.* It has been proposed that this structure interacts with viral and host nucleic acid and protein factors to form a complex to regulate transcription and replication (Zhou, Y. et al.,2006. Therefore it appears to play a significant role in the efficiency of RNA- translation, and virus ability to cause infection, hence the role of 3-UTR in determining the severity of dengue disease seems plausible. The literature reviewed under this study did show considerable intra-serotype diversity at 3-UTR region with greatest variability seen in DEN-4 followed by DEN-1.

A comparative analysis of 3' UTR conducted for DENV isolates from Bangkok, Thailand compared Thai sequences with 61 globally sampled isolates of DENV taken from patients with varying disease severity. Although some genetic variations were found both within and among the serotypes notably at 3' Long Hairpin Stable structure, however these mutations did not show consistent association with the clinical outcome of the DENV infection (Zhou, Y. et al.,2006). Study focusing on terminal 3' 5'UTR sequences of four DEN-2 from Thailand 1998 outbreak strains, showed complete homology for sequences at 5' UTR (highly conserved region) when compared with the prototype virus New Guinea C strain

Fig. 2. The Geographical distribution of mutations in DEN-2 and DEN-3 viruses detected at different genomic loci of isolates from South East Asia
