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HIV-1 causes the loss of CD4 +  T cells via depletion or impairment of their production. The latter involves infection of thymocytes, but the involvement of hematopoietic CD34 +  cells remains unclear even though HIV-positive patients frequently manifest myelosuppression. In order to have a closer look at the impact of HIV-1 on T-lineage differentiation, this study utilized the OP9-DL1 coculture system, which supports  in vitro  T-lineage differentiation of human hematopoietic stem/progenitor cells. In the newly developed  in vitro  OP9-DL1/HIV-1 model, cord-derived CD34 +  cells were infected with CXCR4-tropic HIV-1 NL4−3  and cocultured. The HIV-infected cocultures exhibited reduced CD4 +  T-cell growth at weeks 3–5 post infection compared to autologous uninfected cocultures. Further assays and analyses revealed that CD34 + CD7 + CXCR4 +  cells can be quickly depleted as early as 1 week after infection of the subset, and this was accompanied by the emergence of rare CD34 + CD7 + CD4 +  cells. A subsequent theoretical model analysis suggested potential influence of HIV-1 on the differentiation rate or death rate of lymphoid progenitor cells. These results indicate that CXCR4-tropic HIV-1 strains may impact the dynamics of CD34 + CD7 +  lymphoid progenitor cell pools, presumably leading to impaired T-cell production potential.

HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells