TY - JOUR T1 - HIV disrupts CD34<sup>+</sup> progenitors involved in T-cell differentiation JF - bioRxiv DO - 10.1101/142539 SP - 142539 AU - Tetsuo Tsukamoto Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/09/22/142539.abstract N2 - 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-1NL4-3 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. ER -