HIV causes a chronic infection characterized by depletion of CD4+ T lymphocytes and, at late stages, severe bone marrow abnormalities. Despite the development of drugs that inhibit viral spread, HIV has been difficult to treat because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy and the immune response. We have used CD34+ cells from infected people as well as in vitro studies of wild type HIV to demonstrate infection and killing of CD34+ hematopoietic progenitor cells (HPCs). Importantly, the HPCs that became infected included primitive, multi-potent cells. In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. This application proposes studies, which will determine whether HIV-1 envelope tropism targets progenitor cells with different developmental capacities and whether HIV-1 infects bona fide stem cells.

Public Health Relevance

The overall goal of this research is to develop improved treatments for HIV-infected people by determining which cell types are responsible for persistent disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI086599-02
Application #
8089466
Study Section
Special Emphasis Panel (ZRG1-AARR-D (04))
Program Officer
Embry, Alan C
Project Start
2010-07-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2011
Total Cost
$153,945
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Carter, Christoph C; McNamara, Lucy A; Onafuwa-Nuga, Adewunmi et al. (2011) HIV-1 utilizes the CXCR4 chemokine receptor to infect multipotent hematopoietic stem and progenitor cells. Cell Host Microbe 9:223-234
McNamara, Lucy A; Collins, Kathleen L (2011) Hematopoietic stem/precursor cells as HIV reservoirs. Curr Opin HIV AIDS 6:43-8