title: HIV-1 gp120 impairs the differentiation and survival of cord blood CD34+ HPCs induced to the erythroid lineage.
abstract: Anemia is the most common hematological abnormality in human immunodeficiency virus (HIV)-infected patients. Besides chronic disease, opportunistic infections, nutritional deficiencies and antiretroviral drug toxicity, the direct role of HIV in the development of anemia has not yet been fully investigated. To explore the HIV-related mechanisms involved in the genesis of anemia, we used two experimental designs. In the first, HPCs purified from cord blood were challenged with HIV-1IIIb or recombinant gp120 (rgp120) and then committed to erythrocyte differentiation (EPO-post-treated HPCs). In the second, HPCs were first committed to differentiate towards the erythroid lineage and only afterwards challenged with HIV-1IIIb or rgp120 (EPO-pre-treated HPCs). Our results showed that HPCs and EPO-induced HPCs were not susceptible to HIV-1 infection. In addition, the two experimental designs (EPO post or pre-treated HPCs) independently showed that HIV-1IIIb or rgp120 were able to induce the impairment of survival, proliferation, and differentiation albeit differing in kinetics and extent. Interestingly, the gp120 interaction with CD4 and CXCR4 played a pivotal role in the impairment of erythrocyte differentiation by inducing TGF-b1 expression. These observations reveal an important additional mechanism involved in the genesis of anemia suggesting a complex competition between EPO-positive regulation and HIV-negative priming regarding erythrocyte survival, proliferation and maturation.
authors.affiliation: Microbiology Section of the Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morini
authors.affiliation: Microbiology Section of the Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Musumeci
authors.affiliation: Microbiology Section of the Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Bon
authors.affiliation: Microbiology Section of the Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Miserocchi
authors.affiliation: Histology Section of the Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Alviano
authors.affiliation: Microbiology Section of the Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Longo
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertoldi
authors.affiliation: Immunohematology and Transfusion Medicine Service, S. Orsola-Malpighi Hospital, University of Bologna, Italy.
authors.forename: Claudio V
authors.initials: CV
authors.lastname: Velati
authors.affiliation: Interuniversity Consortium, National Institute of Biostructures and Biosystems (INBB), Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
authors.affiliation: Microbiology Section of the Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Italy.|Interuniversity Consortium, National Institute of Biostructu.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Re
mesh_terms: D000740:Anemia / Q000150:complications*; D018952:Antigens, CD34 / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D041905:Erythroid Cells / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D005312:Fetal Blood / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006021:Glycophorins / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015658:HIV Infections / Q000209:etiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D018952:Antigens, CD34; D015704:CD4 Antigens; C527276:CXCR4 protein, human; D006021:Glycophorins; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D004921:Erythropoietin
keywords: CD34+ HPCs; HIV; apoptosis; erythropoiesis; glycophorin