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HIV-1 persistence in CD4+ T cells with stem cell-like properties
Maria J Buzon1, Hong Sun2, Chun Li3
11] Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
Nature Medicine
|January 14, 2014
Summary
Despite antiretroviral therapy, HIV-1 persists in CD4(+) T memory stem cells (TSCM cells). These cells harbor high viral DNA levels, contributing significantly to the long-term HIV reservoir.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Cellular HIV-1 reservoirs are a major barrier to complete viral eradication.
- The precise location and characteristics of these persistent reservoirs remain incompletely understood.
Purpose of the Study:
- To investigate the role of CD4(+) T memory stem cells (TSCM cells) in harboring persistent HIV-1 during suppressive antiretroviral therapy (ART).
- To determine the contribution of TSCM cells to the overall viral reservoir over time.
Main Methods:
- Analysis of HIV-1 DNA levels in CD4(+) TSCM cells from individuals on suppressive ART.
- Longitudinal assessment of the TSCM cell compartment's contribution to the viral reservoir.
- Phylogenetic studies to evaluate viral persistence within TSCM cells.
Main Results:
- CD4(+) TSCM cells harbor high per-cell levels of HIV-1 DNA during suppressive ART.
- The contribution of TSCM cells to the total viral CD4(+) T cell reservoir increases over time.
- Phylogenetic analyses suggest long-term persistence of HIV-1 quasispecies within TSCM cells.
Conclusions:
- HIV-1 may exploit the stem cell-like properties of TSCM cells for long-term viral persistence.
- TSCM cells represent a critical cellular reservoir contributing to the challenge of HIV-1 eradication.
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