Nucleotide sequence analysis of viral genome related with pathogenesis of dengue hemorrhagic fever

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Comparative nucleotide and deduced amino acid sequences were analyzed for 4 dengue type 2 virus strains isolated from patients with different clinical severities in Nakhon Phanom, Northeast Thailand in 1993, in order to obtain direct evidence for virulent virus theory of the pathogenesis of dengue hemorrhagic fever.The results showed followings : (1) Amino acid sequence of virus-specified proteins classified the isolates into 3 subtypes : subtype 1 was the isolate from the most severe DSS patient, subtype 2 were 2 isolates from DHF patients and 2 isolates from DF patients, and subtype 3 were 3 isolates from DF patients. (2) Secondary structure predicted for the 3'noncoding region (3'NCR) also classified the isolates into 3 subtypcs : subtype 1 was the isolate from DSS patient, subtype 2 were 2 isolates from DHF patients and 3 isolates from DF patients, and subtype 3 were 2 isolates from DF patients. These results indicated that the infection with virus strain possessing subtype 1 amino acid sequence and subtype 1 secondary structure of 3'NCR is expected to lead to severe clinical manifestation, while the infection with virus strains possessing subtype 3 amino acid sequence and subtype 3 secondary structure of 3'NCR is cxpected to be clinically mild. The plaque size formed on LLC-MK2 cells did not correlate with the structure of virus genome but rather with the serological response of the patients.Further studies were carried out on comparative sequence analysis on 4 strains of dengue type 4 virus isolated in Bangkok, Thailand, 1993. The result identified strain-specific amino acid replacements for the isolate from mild DF case as well as the isolate from relatively severe DHF grade II patients. These amino acid replacements were cxpected to influence the nature of the respective proteins. Effect of the observed molecular difference on the biological characteristics of virus isolates and relation to the pathogenesis of DHF remain to be investigated.