Murine Model for Dengue Virus-Induced Lethal Disease with Increased Vascular Permeability

摘要: Lack of an appropriate animal model for dengue virus (DEN), which causes fever and hemorrhagic fever/dengue shock syndrome (DHF/DSS), has impeded characterization the mechanisms underlying disease pathogenesis. The cardinal feature DHF/DSS, severe form DEN infection, is increased vascular permeability. To develop a murine that more relevant to novel strain, D2S10, was generated by alternately passaging non-mouse-adapted strain between mosquito cells mice, thereby mimicking natural transmission cycle mosquitoes humans. After infection with mice lacking interferon receptors died early without manifesting signs paralysis, carried infectious in both non-neuronal neuronal tissues, exhibited In contrast, infected parental developed paralysis at late times after contained detectable levels only central nervous system, displayed normal but not significant serum tumor necrosis factor alpha (TNF-) were produced, neutralization TNF- activity prevented death D2S10-infected mice. Sequence analysis comparing D2S10 its implicated conserved region amino acid residues envelope protein as possible source phenotype. These results demonstrate may be one several key mediators DEN-induced This report represents advance models disease, it begins provide mechanistic insights into vivo.