Molecular and viral research on dengue hemorrhagic fever

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In order to elucidate various virus and host factors that are relevant to the development of dengue hemorrhagic fever, we conducted a three-year research project. We isolated a number of dengue virus strains during dengue epidemic in Bangladesh, the Philippines, and Vietnam and determined nucleotide sequences of the virus strains. The data was compared with each other as well as the sequences obtained in conventional data base. We witnessed the genotype shift of dengue virus 2 in the Philippines during the early 2000s from local strain to cosmopolitan strain. While in Bangladesh and Vietnam, dengue viruses evolved locally and caused periodic epidemics in the countries. In the comparisons made with viruses from dengue hemorrhagic fever and dengue fever, we could not detect any significant differences between the two groups. In the flow cytometry analysis, we clearly demonstrated that dengue virus can infect peripheral B cells and NK cells suggesting the target of dengue virus in humans is not always on a particular cell group but the virus can choose the target cells according to its affinity to each virus group.This idea was further strengthened later by the fact that two distinct virus strains were isolated from one patient by using different cell lines for isolation. One virus stain was isolated by mosquito cells and grow well in the cells but not human B cell line. While the other virus was isolated by K562, a culture cell line form human monocyte, grow well in B cell lines. Those two viruses possessed an amino acid alternation in E protein, suggesting a determinant of cell tropism. It is very likely that dengue virus population gap may have some effect to determine dengue virus pathogenesis in human infection. Further clarification of the importance of this dengue virus population gap is necessary to understand the mechanism to determine the severity in dengue virus infections in humans.