Epitopes described in "Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice."

Article Authors:Smita Jaiswal; Todd Pearson; Heather Friberg; Leonard D Shultz; Dale L Greiner; Alan L Rothman; Anuja Mathew
Article Title:Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice.
Reference Detail
Reference ID:1017734
Abstract:BACKGROUND: The lack of a suitable animal model to study viral and immunological mechanisms of human dengue disease has been a deterrent to dengue research. METHODOLOGY/PRINCIPAL FINDINGS: We sought to establish an animal model for dengue virus (DENV) infection and immunity using non-obese diabetic/severe combined immunodeficiency interleukin-2 receptor gamma-chain knockout (NOD-scid IL2rgamma(null)) mice engrafted with human hematopoietic stem cells. Human CD45(+) cells in the bone marrow of engrafted mice were susceptible to in vitro infection using low passage clinical and established strains of DENV. Engrafted mice were infected with DENV type 2 by different routes and at multiple time points post infection, we detected DENV antigen and RNA in the sera, bone marrow, spleen and liver of infected engrafted mice. Anti-dengue IgM antibodies directed against the envelope protein of DENV peaked in the sera of mice at 1 week post infection. Human T cells that developed following engraftment of HLA-A2 transgenic NOD-scid IL2rgamma(null) mice with HLA-A2(+) human cord blood hematopoietic stem cells, were able to secrete IFN-gamma, IL-2 and TNF-alpha in response to stimulation with three previously identified A2 restricted dengue peptides NS4b 2353((111-119)), NS4b 2423((181-189)), and NS4a 2148((56-64)). CONCLUSIONS/SIGNIFICANCE: This is the first study to demonstrate infection of human cells and functional DENV-specific T cell responses in DENV-infected humanized mice. Overall, these mice should be a valuable tool to study the role of prior immunity on subsequent DENV infections.
Affiliations:Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Reference Type:Literature
PubMed ID:19802382
Journal:PLoS One
Journal Volume:4
Article Pages:e7251
Journal ISSN:1932-6203
Article Chemical List:HLA-A2 Antigen;Interleukin-2;Peptides;RNA
Article MeSH List:Animals; Dengue(immunology); Dengue Virus(immunology); Fetal Blood(cytology; virology); HLA-A2 Antigen(immunology); Hematopoiesis; Hematopoietic Stem Cells(cytology; virology); Humans; Interleukin-2(immunology); Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID(immunology); Peptides(chemistry); RNA(metabolism)
Curation Last Updated:2015-06-05 01:53:26