Abstract

The applicant proposes studies to evaluate the hypothesis that HIV infection leads to destruction or dysfunction of the bone marrow microenvironment such that multilineage hematopoiesis is altered. The Investigator has developed a human bone marrow microaggregate culture system that supports multi-lineage and lineage committed hematopoiesis in vitro for up to 8 days, and is permissive for HIV infection. Results from experiments assessing the effects of HIV infection in this system will be compared to data obtained from the evaluation of bone marrow from HIV infected individuals, and also correlated with evaluation of bone marrow cell proliferation and turnover in HIV and normal subjects, using the introduction of deuterated glucose. The Investigator will use these studies to determine if HIV infection suppresses multilineage hematopoiesis by inhibiting proliferation, differentiation or survival of hematopoietic progenitor cells, and will also investigate potential mechanisms for this inhibition, including alteration of cytokines or disruption of surface interactions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI040312-09
Application #
6751875
Study Section
Special Emphasis Panel (ZRG1-AARR-1 (01))
Program Officer
Bridges, Sandra H
Project Start
1996-04-01
Project End
2005-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
9
Fiscal Year
2004
Total Cost
$398,365
Indirect Cost

  Institution

Name
J. David Gladstone Institutes
Department
Type
DUNS #
099992430
City
San Francisco
State
CA
Country
United States
Zip Code
94158

  Publications

Ladell, Kristin; Hazenberg, Mette D; Fitch, Mark et al. (2015) Continuous Antigenic Stimulation of DO11.10 TCR Transgenic Mice in the Presence or Absence of IL-1?: Possible Implications for Mechanisms of T Cell Depletion in HIV Disease. J Immunol 195:4096-105
Seu, Lillian; Ortiz, Gabriel M; Burt, Trevor D et al. (2014) Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4(+) T cell recovery after the initiation of antiretroviral therapy for HIV disease. AIDS Res Ther 11:27
Dunham, Richard M; Vujkovic-Cvijin, Ivan; Yukl, Steven A et al. (2014) Discordance between peripheral and colonic markers of inflammation during suppressive ART. J Acquir Immune Defic Syndr 65:133-41
Vujkovic-Cvijin, Ivan; Dunham, Richard M; Iwai, Shoko et al. (2013) Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med 5:193ra91
Miller, Corey N; Hartigan-O'Connor, Dennis J; Lee, Myeong Sup et al. (2013) IL-7 production in murine lymphatic endothelial cells and induction in the setting of peripheral lymphopenia. Int Immunol 25:471-83
Seu, Lillian; Ortiz, Gabriel M; Epling, Lorrie et al. (2013) Higher CD27+CD8+ T cells percentages during suppressive antiretroviral therapy predict greater subsequent CD4+ T cell recovery in treated HIV infection. PLoS One 8:e84091
Baum, Paul D; Young, Jennifer J; Schmidt, Diane et al. (2012) Blood T-cell receptor diversity decreases during the course of HIV infection, but the potential for a diverse repertoire persists. Blood 119:3469-77
Sacre, Karim; Hunt, Peter W; Hsue, Priscilla Y et al. (2012) A role for cytomegalovirus-specific CD4+CX3CR1+ T cells and cytomegalovirus-induced T-cell immunopathology in HIV-associated atherosclerosis. AIDS 26:805-14
Seu, L; Burt, T D; Witte, J S et al. (2012) Variations in the heme oxygenase-1 microsatellite polymorphism are associated with plasma CD14 and viral load in HIV-infected African-Americans. Genes Immun 13:258-67
Kiem, Hans-Peter; Jerome, Keith R; Deeks, Steven G et al. (2012) Hematopoietic-stem-cell-based gene therapy for HIV disease. Cell Stem Cell 10:137-47

Showing the most recent 10 out of 49 publications