This project is to establish a new humanized mouse model for the study of immune responses to HIV infection and vaccination. The model utilizes severely immunocompromised mice reconstituted with human thymic and liver tissue, which establishes human lymphocytic and monocytic populations susceptible to HIV infection. We have immunized the animals against HIV-1 CD4+ T cell epitopes and are now studying immune responses. An immediate goal is to determine whether the presence of HIV-1-specific CD4+ memory cells mount effective immune responses to control HIV infection, or act as targets for infection and cause an increase in susceptibility.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2012
Total Cost
$311,382
Indirect Cost
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State
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Lavender, Kerry J; Williamson, Brandi N; Saturday, Greg et al. (2018) Pathogenicity of Ebola and Marburg Viruses Is Associated With Differential Activation of the Myeloid Compartment in Humanized Triple Knockout-Bone Marrow, Liver, and Thymus Mice. J Infect Dis :
Hasenkrug, Kim J; Chougnet, Claire A; Dittmer, Ulf (2018) Regulatory T cells in retroviral infections. PLoS Pathog 14:e1006776
Lavender, Kerry J; Pace, Craig; Sutter, Kathrin et al. (2018) An advanced BLT-humanized mouse model for extended HIV-1 cure studies. AIDS 32:1-10
Van Dis, Erik S; Moore, Tyler C; Lavender, Kerry J et al. (2016) No SEVI-mediated enhancement of rectal HIV-1 transmission of HIV-1 in two humanized mouse cohorts. Virology 488:88-95
Lavender, Kerry J; Gibbert, Kathrin; Peterson, Karin E et al. (2016) Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo. J Virol 90:6001-6013
Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B et al. (2016) Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID ""Meet the Experts"" 2015 Workshop Summary. AIDS Res Hum Retroviruses 32:109-19
Harper, Michael S; Guo, Kejun; Gibbert, Kathrin et al. (2015) Interferon-? Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms. PLoS Pathog 11:e1005254
Lavender, Kerry J; Pang, Wendy W; Messer, Ronald J et al. (2013) BLT-humanized C57BL/6 Rag2-/-?c-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection. Blood 122:4013-20