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. 2005 Nov;79(21):13797-9.
doi: 10.1128/JVI.79.21.13797-13799.2005.

Dengue fever in humanized NOD/SCID mice

Dennis A Bente  1 , Michael W Melkus, J Victor Garcia, Rebeca Rico-Hesse
Affiliations

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.
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.
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.
See this image and copyright information in PMC

References

    1. An, J., J. Kimura-Kuroda, Y. Hirabayashi, and K. Yasui. 1999. Development of a novel mouse model for dengue virus infection. Virology 263:70-77. - PubMed
    1. Blaney, J. E., Jr., C. T. Hanson, K. A. Hanley, B. R. Murphy, and S. S. Whitehead. 4. October 2004, posting date. Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2. BMC Infect. Dis. 4:39. [Online.] doi:10.1186/1471-2334-4-39. - DOI - PMC - PubMed
    1. Cologna, R., P. M. Armstrong, and R. Rico-Hesse. 2005. Selection for virulent dengue viruses occurs in humans and mosquitoes. J. Virol. 79:853-859. - PMC - PubMed
    1. Cravens, P. D., M. W. Melkus, A. Padgett-Thomas, M. Islas-Ohlmayer, M. del P. Martin, and J. V. Garcia. 2005. Development and activation of human dendritic cells in vivo in a xenograft model of human hematopoiesis. Stem Cells 23:264-278. - PubMed
    1. Halstead, S. B., and J. Deen. 2002. The future of dengue vaccines. Lancet 360:1243-1245. - PubMed

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