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

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 T-lineage differentiation of human hematopoietic stem/progenitor cells. In the newly developed OP9-DL1/HIV-1 model, cord-derived CD34 cells were infected with CXCR4-tropic HIV-1 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 CD34CD7CXCR4 cells can be quickly depleted as early as 1 week after infection of the subset, and this was accompanied by the emergence of rare CD34CD7CD4 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 CD34CD7 lymphoid progenitor cell pools, presumably leading to impaired T-cell production potential.