Work

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

Year: 2017

Type: article

Abstract: Chronic human immunodeficiency virus-1 (HIV-1) infection in patients leads to multilineage 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. Author summaryMulti-lineage hematopoietic abnormalities generally occur during chronic infection which results in a disorder of human leukocyte development and differentiation, contributing to human immunodeficiency virus-1 (HIV-1)-infection induced immune-pathogenesis in AIDS patients.Although successful antiretroviral therapy can reduce plasma viral loads to undetectable levels and ameliorate HIV-1-associated hemato-suppression, immune cell development is only partially restored.The mechanism for the abnormal hematopoiesis occurring during chronic HIV-1 infection remains unclear.HIV-1 infection may directly or indirectly functionally impair hematopoietic progenitors by either viral products or induction of persistent inflammatory responses, leading to hematopoiesis

Source: PLoS Pathogens

DOI: 10.1371/journal.ppat.1006505