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Dengue virus infection and virus‐specific immune responses in humanized NOD‐scid IL2rgammanull mice
Author(s) -
Jaiswal Smita,
Pearson Todd,
Friberg Heather,
Shultz Leonard D,
Greiner Dale L,
Rothman Alan L,
Mathew Anuja
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.494
Subject(s) - dengue virus , humanized mouse , immune system , virology , biology , immunology , dengue fever , dengue vaccine , bone marrow , nod , spleen , immunity , in vivo , microbiology and biotechnology
A major obstacle in studying the pathogenesis of dengue virus infection and the development of a successful dengue vaccine is the lack of a suitable animal model. We sought to establish an animal model for dengue virus (DENV) infection and immunity using humanized non‐obese diabetic/severe combined immunodeficiency interleukin‐2 receptor γ‐chain knockout (NOD‐ scid IL2rγ null ) mice, which develop a functional human adaptive immune system following engraftment with human CD34+ hematopoietic stem cells. Human CD45+ cells in the bone marrow of reconstituted mice were susceptible to DENV infection in vitro. Reconstituted mice were next infected with DENV type 2 to assess in vivo viral replication and the induction of human DENV‐specific immune responses. At multiple time points post infection, we detected DENV antigen and RNA in the serum, bone marrow, spleen and liver of infected reconstituted mice. In addition, human T cells from infected engrafted NOD‐ scid IL2rγ null mice generated a DENV‐specific IFNγ response. This is the first study to identify DENV‐infected human cells and demonstrate functional DENV‐specific T cell responses in DENV‐infected humanized mice. Overall, these mice should be a valuable tool to study DENV infection and immunity. This project was supported by grant A50230 from the WHO and an institutional Diabetes Endocrinology Research Center (DERC) grant DK52530 from the NIH.