Humanized mice show clinical signs of dengue fever according to infecting virus genotype

Javier Mota, Rebeca Rico-Hesse

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

We demonstrated that the infection of humanized NOD-scid IL2rγ null mice with different strains (representing the four genotypes) of dengue virus serotype 2 (DEN-2) can induce the development of human-like disease, including fever, viremia, erythema, and thrombocytopenia. Newborn mice were irradiated and received transplants by intrahepatic inoculation of human cord blood-derived hematopoietic progenitor cells (CD34+). After 6 weeks, mouse peripheral blood was tested by flow cytometry to determine levels of human lymphocytes (CD45+ cells); rates of reconstitution ranged from 16 to 80% (median, 52%). Infection (with approximately 106 PFU, the equivalent of a mosquito bite) of these humanized mice with eight low-passage-number strains produced a high viremia extending to days 12 to 18 postinfection. We observed a significant decrease in platelets at day 10 in most of the mice and an increase in body temperature (fever) and erythema (rash) in comparison with humanized mice inoculated with cell culture medium only. Comparison of Southeast (SE) Asian and other genotype viruses (American, Indian, and West African) in this model showed significant differences in magnitude and duration of viremia and rash, with the SE Asian viruses always being highest. Indian genotype viruses produced lower viremias and less thrombocytopenia than the others, and West African (sylvatic) viruses produced the shortest periods of viremia and the lowest rash measurements. These results correlate with virulence and transmission differences described previously for primary human target cells and whole mosquitoes and may correlate with epidemiologic observations around the world. These characteristics make this mouse model ideal for the study of dengue pathogenesis and the evaluation of vaccine attenuation and antivirals.

Original languageEnglish (US)
Pages (from-to)8638-8645
Number of pages8
JournalJournal of virology
Volume83
Issue number17
DOIs
StatePublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint

Dive into the research topics of 'Humanized mice show clinical signs of dengue fever according to infecting virus genotype'. Together they form a unique fingerprint.

Cite this