Abstract
CCR5-tropic strains of HIV-1 infect and deplete memory CD4+ T cells, and therefore are considered critical in development of AIDS. In contrast, the impact of CXCR4-tropic HIV-1 strains on the disease is not well understood. CXCR4 is known for its role in the hematopoiesis in the bone marrow and T cell differentiation in the thymus, and therefore its expression on hematopoietic progenitors/precursors is considered essential. Here the authors utilized the OP9-DL1 coculture system that supports in vitro differentiation of human CD34+ hematopoietic stem/progenitor cells to T-lineage cells. Using the system, the present study established an in vitro model to analyze the differentiation process of human CD34+ cells in the presence of HIV-1. HIV-infected cocultures showed sustained HIV replication for five weeks and impaired cell growth. Moreover, HIV-infected samples showed a partial loss of CD34+CD7hiCXCR4hi cells compared to uninfected samples during the coculture. These results highlight the possible role of CXCR4-tropic HIV-1 strains in the AIDS pathogenesis by disrupting the CXCR4+ cell pools in hematopoiesis and T cell differentiation.