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Hematopoietic stem cells in HIV disease
1AIDS Research Center and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. scadden.david@mgh.harvard.edu
Journal of the National Cancer Institute. Monographs
|February 7, 2001
Summary
Hematopoietic stem cells are resistant to direct human immunodeficiency virus type-1 (HIV) infection, despite playing a role in HIV-related conditions. These stem cells can be a resource for future AIDS cellular therapies.
Area of Science:
- Hematology
- Virology
- Immunology
Background:
- Hematopoietic stem cells (HSCs) are hypothesized targets for human immunodeficiency virus type-1 (HIV) infection, potentially limiting immune cell production.
- Emerging data show HSC dysfunction in HIV disease and highlight new T-cell generation for immune recovery during antiretroviral therapy.
Purpose of the Study:
- To investigate the susceptibility of HSCs to HIV infection and their role in HIV pathogenesis.
- To clarify the indirect effects of HIV on HSC physiology and their potential as a cellular therapy resource for Acquired Immunodeficiency Syndrome (AIDS).
Main Methods:
- Review of existing data on HSCs and HIV interaction.
- Analysis of HSC resistance to direct HIV infection despite surface receptor presence.
- Examination of stem transduction using modified HIV constructs.
Main Results:
- HSCs are highly resistant to direct HIV infection, even with HIV receptors on their surface.
- HIV's effects on HSC physiology appear to be indirect.
- Stem transduction is achievable with engineered HIV constructs, suggesting potential for gene therapy.
Conclusions:
- HSCs are not directly infectible by HIV, challenging the hypothesis of direct infection as a cause of immune dysfunction.
- HSCs are implicated in HIV-related cytopenias but are spared direct viral assault.
- HSCs represent a potential cellular resource for developing novel cellular therapies for AIDS.