Dengue is one of the most important mosquito-borne viral illnesses. The first DHF outbreak was reported from the Philippines in 1953. Initially it was endemic only in Southeast Asia and the Western Pacific regions. After about 50 years from the first outbreak, it spread globally to almost every continent including North and South America, Australia and Africa. The majority of cases during the 50s to 80s were children, but today the disease affects both children and adults of all age groups. The disease is caused by dengue viruses that have four serotypes: dengue 1, dengue 2, dengue 3 and dengue 4. Primary infection usually results in milder illness, while more severe disease occurs in cases of repeated infection with different serotypes. In this paper clinical manifestations and management of dengue/DHF/DSS are summarized.

Objective:To study evolutionary relationship of the 5’untranslated regions (5’UTRs) in low passage dengue3 viruses (DEN3) isolated from hospitalized children with different clinical manifestations in Bangkok during 24 year-evolution (1977-2000) comparing to the DEN3 prototype (H87).Methods:The 5’UTRs of these Thai DEN3 and the H87 prototype were amplified by RT-PCR and sequenced. Their multiple sequence alignments were done by Codon Code Aligner v 4.0.4 software and their RNA secondary structures were predicted by MFOLD software. Replication of five Thai DEN3 candidates comparing to the H87 prototype were done in human (HepG2) and the mosquito (C6/36) cell lines.Results:Among these Thai DEN3, the completely identical sequences of their first 89 nucleotides, their high-order secondary structure of 5’UTRs and three SNPs including the predominant C90T, and two minor SNPs including A109G and A112G were found. The C90T of Thai DEN3, Bangkok isolates was shown predominantly before 1977. Five Thai DEN3 candidates with the predominant C90T were shown to replicate in human (HepG2) and the mosquito (C6/36) cell lines better than the H87 prototype. However, their highly conserved sequences as well as SNPs of the 5’UTR did not appear to correlate with their disease severity in human.Conclusions:Our findings highlighted evolutionary relationship of the completely identical 89 nucleotide sequence, the high-order secondary structure and the predominant C90T of the 5’UTR of these Thai DEN3 during 24 year-evolution further suggesting to be their genetic markers and magic targets for future research on antiviral therapy as well as vaccine approaches of Thai DEN3.

Dengue virus (DENV) is a leading cause of morbidity and mortality in most tropical and subtropical areas of the world. Dengue virus infection induces specific CD4+CD8– and CD8+CD4– T cells in humans. In primary infection, T-cell responses to DENV are serotype cross-reactive, but the highest response is to the serotype that caused the infection. The epitopes recognized by DENV-specific T cells are located in most of the structural and non-structural proteins, but NS3 is the protein that is most dominantly recognized. In patients with dengue hemorrhagic fever (DHF) caused by secondary DENV infection, T cells are highly activated in vivo. These highly activated T cells are DENV-specific and oligoclonal. Multiple kinds of lymphokines are produced by the activated T cells, and it has been hypothesized that these lymphokines are responsible for induction of plasma leakage, one of the most characteristic features of DHF. Thus, T-cells play important roles in the pathogenesis of DHF and in the recovery from DENV infection.

Objective: To study evolutionary relationship of the 5'untranslated regions (5'UTRs) in low passage dengue3 viruses (DEN3) isolated from hospitalized children with different clinical manifestations in Bangkok during 24 year-evolution (1977-2000) comparing to the DEN3 prototype (H87). Methods: The 5'UTRs of these Thai DEN3 and the H87 prototype were amplified by RT-PCR and sequenced. Their multiple sequence alignments were done by Codon Code Aligner v 4.0.4 software and their RNA secondary structures were predicted by MFOLD software. Replication of five Thai DEN3 candidates comparing to the H87 prototype were done in human (HepG2) and the mosquito (C6/36) cell lines. Results: Among these Thai DEN3, the completely identical sequences of their first 89 nucleotides, their high-order secondary structure of 5'UTRs and three SNPs including the predominant C90T, and two minor SNPs including A109G and A112G were found. The C90T of Thai DEN3, Bangkok isolates was shown predominantly before 1977. Five Thai DEN3 candidates with the predominant C90T were shown to replicate in human (HepG2) and the mosquito (C6/36) cell lines better than the H87 prototype. However, their highly conserved sequences as well as SNPs of the 5'UTR did not appear to correlate with their disease severity in human. Conclusions: Our findings highlighted evolutionary relationship of the completely identical 89 nucleotide sequence, the high-order secondary structure and the predominant C90T of the 5'UTR of these Thai DEN3 during 24 year-evolution further suggesting to be their genetic markers and magic targets for future research on antiviral therapy as well as vaccine approaches of Thai DEN3.