Towards a Cure for HIV: the identification and characterization of HIV reservoirs in optimally treated people.
Onafuwa-Nuga A, McNamara LA, Collins KL. Cell Research 2010; Sept. 28, Pub ahead of print.
Studies of viral load decay during HAART have suggested the existence of other reservoirs than latently infected CD4+ T cells. Several experiments have demonstrated that multipotent hematopoietic stem/precursor cells (HSPCs) can become infected with HIV-1.
Most multipotent hematopoietic precursor cells express CD34, a cell surface marker found on HSPCs ranging from hematopoietic stem cells (HSCs) to progenitor cells committed to differentiation. CD34+ populations that lack CD38 and express CD133 are enriched for multipotent progenitor cells. A proportion of CD34+ cells express the HIV receptors CD4, CXCR4 and CCR5.
In this paper, the authors show evidence that CD34+ HSPCs can be infected in vitro by HIV. Importantly, they also demonstrate that HIV can establish latency in HSPCs infected in vitro.
To determine whether HIV infects CD34+ bone marrow HSPCs in vivo, they obtained bone marrow from different HIV-infected patients. CD34+ cells from donors with undetectable plasma viremia for more than 6 months did not express detectable amounts of HIV Gag by flow cytometry. In one donor, HIV Gag expression was induced upon myeloid differenciation of CD34+. These findings provide evidence that CD34+ cells could harbor latent HIV in some patients.
HIV DNA could also be amplified from CD34+ bone marrow cells from more than 40% of patients with plasma viremia <48 copies/ml after more than 6 months of effective HAART.
On the contrary, HIV DNA could not be detected from bone marrow depleted for CD34+ cells.
These results show that CD34+ cells might act as a long-lived reservoir for HIV. Additional studies are needed to clarify which subset of CD34+ cells harbor HIV genomes in vivo and whether latently infected CD34+ cells contribute to residual viremia in patients on HAART.
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Key words: CD34, cure, eradication stem cells, hiv, persistence, reservoirs