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.
Keywords: CD34+ HPCs; HIV; apoptosis; erythropoiesis; glycophorin.