PT  - JOURNAL ARTICLE
AU  - Tetsuo Tsukamoto
AU  - Seiji Okada
TI  - HIV persistence alters CXCR4 expression patterns in OP9-DL1-mediated differentiation of in vitro infected human cord blood CD34<sup>+</sup> cells
AID  - 10.1101/142539
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 142539
4099  - http://biorxiv.org/content/early/2017/05/26/142539.short
4100  - http://biorxiv.org/content/early/2017/05/26/142539.full
AB  - 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.