4 years ago

HIV-1 infection depletes human CD34<sup>+</sup>CD38<sup>-</sup> hematopoietic progenitor cells via pDC-dependent mechanisms

Zheng Zhang, Lishan Su, Liguo Zhang, Liang Cheng, Juanjuan Zhao, Bo Tu, Enqiang Qin, Qi Jiang, Xin Zhang, Guangming Li, Sheng Kan

by Guangming Li, Juanjuan Zhao, Liang Cheng, Qi Jiang, Sheng Kan, Enqiang Qin, Bo Tu, Xin Zhang, Liguo Zhang, Lishan Su, Zheng Zhang

Chronic human immunodeficiency virus-1 (HIV-1) infection in patients leads to multi-lineage hematopoietic abnormalities or pancytopenia. The deficiency in hematopoietic progenitor cells (HPCs) induced by HIV-1 infection has been proposed, but the relevant mechanisms are poorly understood. We report here that both human CD34+CD38- early and CD34+CD38+ intermediate HPCs were maintained in the bone marrow (BM) of humanized mice. Chronic HIV-1 infection preferentially depleted CD34+CD38- early HPCs in the BM and reduced their proliferation potential in vivo in both HIV-1-infected patients and humanized mice, while CD34+CD38+ intermediate HSCs were relatively unaffected. Strikingly, depletion of plasmacytoid dendritic cells (pDCs) prevented human CD34+CD38- early HPCs from HIV-1 infection-induced depletion and functional impairment and restored the gene expression profile of purified CD34+ HPCs in humanized mice. These findings suggest that pDCs contribute to the early hematopoietic suppression induced by chronic HIV-1 infection and provide a novel therapeutic target for the hematopoiesis suppression in HIV-1 patients.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.ppat.1006505

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