17th International AIDS Conference Mexico City, Mexico - August 13 - 18, 2008

HUMANIZED Rag2-/- γ c-/- MICE: A MODEL FOR HIV-1 ANTIBODY RESPONSES AND ANTIRETROVIRAL THERAPY INVESTIGATION

Int Conf AIDS. 2008 Aug 13-18;17 Abstract No. MOAA0102

K. Sango ¹, A. Joseph¹, S. Buhl², M. Patel¹, K. Osiecki¹, J. Ciano¹, H. Goldstein^1
1Albert Einstein College of Medicine, Microbiology and Immunology, Bronx, United States, ²Albert Einstein College of Medicine, Cell Biology, Bronx, United States

BACKGROUND: While studies in non-human primates are invaluable, a small animal model susceptible to HIV-1 infection, with a functional human immune system would be useful. Humanized Rag2-/- γ c-/- mice have emerged as a model for studying HIV-1 infection and immune responses in vivo, since they develop de novo, human, functional T, B, monocytic and dendritic cells following transplantation with human hematopoietic stem cells.

METHODS: We are testing the ability of these reconstituted mice to mount anti-HIV-1 humoral responses, as well as the efficacy of antiretroviral therapy using a novel HIV-infection approach that employs the intrasplenic route, which resulted in high levels of HIV-1 infection.

RESULTS: Following infection, there was depletion of the human CD4+ T cells, paralleled with a significant increase in the levels of CD8+ T cells. More importantly, HIV-1 specific human IgG and IgM against HIV-1 gp120 and Gag proteins were detected in the plasma of the inoculated mice. We found that there was a significant negative correlation between the levels of HIV infection and CD4+ depletion. There was also a highly significant correlation between the reconstitution of CD19+ B-cells prior to the infection and anti-Gag IgG. Anti-gp120 IgG production was correlated with the levels of CD8+ cells and inversely associated with the levels of CD4+ cells following the infection. In addition, anti-gp120 IgG levels were also positively correlated with HIV-1 virus titer, as measured by limiting dilution co-culture. We are now testing these mice in their ability to control the infection while receiving highly active antiretroviral therapy (HAART).

CONCLUSIONS: We demonstrate here that humanized Rag2-/- γ c-/- mice are able to mount anti-HIV-1 humoral responses after intrasplenic infection and can serve as a valuable in vivo infection model to study HIV-1 pathogenesis, immunology, virology and treatments.

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2008-08-13
MOAA0102

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