Abstract

This project resulted in two peer-reviewed journal publications in FY2014. We established an improved 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. The mice support both intravenous and mucosal HIV infection and develop HIV-specific B and T cell immunity. A distinct advantage of this model is that the mice do not develop graft versus host disease and can therefore be used in long-term studies of HIV infection not previously possible.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001141-04
Application #
8946512
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
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  Publications

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
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
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