Genetic variation in the 3 ' non-coding region of dengue viruses

The 3' non-coding region (3'NCR) of strains of dengue 1 (DEN 1), DEN 2, DEN 3, and DEN 4 viruses, isolated in different geographical regions, was sequ enced and compared to published sequences of the four dengue viruses. A tot al of 50 DEN 2 strains was compared: 7 West African strains, 3 Indonesian m osquito strains, 1 Indonesian macaque isolate, and 39 human isolates from S outheast Asia, the South Pacific, and the Caribbean and Americas. Nucleotid e sequence alignment revealed few deletions and no repeat sequences in the 3' NCR of DEN 2 viruses and showed that much of the 3' NCR was well conserv ed. The strains could be divided into two groups, sylvatic and human/mosqui to/macaque, based on nucleotide sequence homology. A hypervariable region w as identified immediately following the NS5 stop codon, which involved a 2- 10 nucleotide deletion in human, mosquito, and macaque isolates compared wi th the sylvatic strains. The DEN 2 3'NCR was also compared with 3'NCR seque nces from strains of DEN 1, DEN 3, and DEN 4 viruses. DEN 1 was found to ha ve four copies of an eight nucleotide imperfect repeat following the NS5 st op codon, while DEN 4 virus had a deletion of 75 nucleotides in the 3'NCR. We propose that the variation in nucleotide sequence in the 3'NCR may have evolved as a function of DEN virus transmission and replication in differen t mosquito and non-human primate/human host cycles. The results from this s tudy are consistent with the hypothesis that DEN viruses arose from sylvati c progenitors and evolved into human epidemic strains. However, the data do not support the hypothesis that variation in the 3'NCR correlates with DEN virus pathogenesis. (C) 2001 Academic Press.