Dengue-3 virus genomic differences that correlate with in vitro phenotype on a human cell line but not with disease severity.

We compared the full genome sequence of nine clinical isolates of dengue virus obtained during an epidemic of dengue-3 in French Polynesia in 1989, from patients with various presentations of disease. The isolates, all belonging to Genotype I, had 25 amino acid substitutions. There was no association with disease severity. When cultured in the K562 human erythroleukemia cell line, the isolates induced a range of cell growth inhibitions that was not associated with the degree of disease severity. By contrast, some substitutions--charge changes in NS1 and NS5, side-chain differences in NS1, loss of the E-153 potential glycosylation site, and 11 nucleotide insertions in the 3'UTR--that have been suggested to result in an increase or attenuation of dengue infection, appeared to be associated with the level of inhibition. These data represent the first documented study of an association between differences in the full dengue-3 genome of clinical isolates and the in vitro phenotype of these isolates on a human cell line.

Structure-activity relationships of dengue antiviral polycyclic quinones.

The virucidal and antiviral photoactivities of three compounds, hypericin, tetrabromohypericin and gymnochrome B, were evaluated against dengue viruses. All the three products were active, and both the virucidal and antiviral activities were enhanced by light. Gymnochrome B was more potent than hypericin and tetrabromohypericin. The presence of the side chains on the hypericin core of gymnochromes appears to be beneficial for both virucidal and antiviral activities. This enhanced activity is likely to be linked to a complementary mechanism independent of photoactivation.

Comparison of dengue-1 virus envelope glycoprotein gene sequences from French Polynesia.

Dengue (DEN) is the leading arboviral infection of humans, with 100 million cases annually in the tropical areas of the world. The recent severe DEN-1 epidemic in French Polynesia in 2001, with an incidence rate of 16% and more than 45% of the cases with dengue hemorrhagic fever/dengue shock syndrome among 1,400 hospitalized children and eight fatalities, led us to study this new circulating strain. The entire envelope (E) gene of two French Polynesian DEN-1 virus isolates from the two epidemics of 1988-1989 (FP89) and 2001 (FP01) were sequenced and compared with 29 published DEN-1 virus E gene sequences. Phylogenetic relationships showed that the FP89 strain belonged to genotype V and the FP01 strain to genotype IV based on studies on the same region of DEN-1 virus genome (1,485 nucleotides). The recent dengue epidemic in French Polynesia in 2001 was probably due to the introduction of a new DEN-1 virus from Southeast Asia, since the minimum nucleotide divergence was 3.3% with A88, the Indonesian strain isolated in 1988 in Jakarta.