Dengue fever in humanized NOD/SCID mice - PubMed (original) (raw)

Dengue fever in humanized NOD/SCID mice

Dennis A Bente et al. J Virol. 2005 Nov.

Abstract

The increased transmission and geographic spread of dengue fever (DF) and its more severe presentation, dengue hemorrhagic fever (DHF), make it the most important mosquito-borne viral disease of humans (50 to 100 million infections/year) (World Health Organization, Fact sheet 117, 2002). There are no vaccines or treatment for DF or DHF because there are no animal or other models of human disease; even higher primates do not show symptoms after infection (W. F. Scherer, P. K. Russell, L. Rosen, J. Casals, and R. W. Dickerman, Am. J. Trop. Med. Hyg. 27:590-599, 1978). We demonstrate that nonobese diabetic/severely compromised immunodeficient (NOD/SCID) mice xenografted with human CD34+ cells develop clinical signs of DF as in humans (fever, rash, and thrombocytopenia), when infected in a manner mimicking mosquito transmission (dose and mode). These results suggest this is a valuable model with which to study pathogenesis and test antidengue products.

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Figures

FIG. 1.

Signs of dengue virus infection in humanized NOD/SCID mice. (a) Thrombocytopenia and erythema in infected mice by day 8 (means and standard errors of the means); platelet levels in nonreconstituted, infected and noninfected (“normal”; n = 9) versus reconstituted, infected (n = 6); and erythema development in the latter group. O.D., optical density. (b) Viremia and fever on days 1 to 18 (mean and standard error) in mice reconstituted with human CD34+ cells. (c) Comparison of rashes on the backs of shaved mice. The nonreconstituted, infected mouse is on the left, and the reconstituted, infected mouse is on the right (both day 7 postinfection).

FIG. 2.

Comparison of dengue virus RNA in reconstituted, infected NOD/SCID mice (hu-SCID) and nonreconstituted, infected NOD/SCID mice (SCID) on day 8. Virus positive-strand RNA was estimated in each organ (samples in triplicate), using quantitative, real-time RT-PCR, as described in reference . The dotted line reflects the limit of detection: approximately 60 genome equivalents per organ sample.

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Dengue fever in humanized NOD/SCID mice - PubMed (original) (raw)