HIV disrupts CD34+progenitors involved in T-cell differentiation

Abstract

AbstractHIV-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-1NL4-3and 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.