HIV disrupts CD34+progenitors involved in T-cell differentiation

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 other cells including haematopoietic CD34 + cells remains unclear even though HIV-positive patients frequently manifest myelosuppression. This study utilised the OP9-DL1 coculture system, which supports in vitro T-lineage differentiation of human haematopoietic stem/progenitor cells. Cord-derived CD34 + cells were infected with CXCR4-tropic HIV-1 NL4-3 and cocultured. HIV-infected cocultures exhibited sustained viral replication for 5 weeks, as well as reduced CD4 + T-cell growth at weeks 3–5. It was further revealed that CD34 + CD7 + CXCR4 + cells can be quickly depleted as early as in 1 week after infection of the subset, and this was accompanied by the emergence of CD34 + CD7 + CD4 + cells. These results indicate that CXCR4-tropic HIV-1 strains may disrupt CD34 + CD7 + lymphoid progenitor cell pools, presumably leading to impaired T-cell production potential.