HUMAN IMMUNODEFICIENCY VIRUS-1 INFECTION INTERRUPTS THYMOPOIESIS AND MULTILINEAGE HEMATOPOIESIS IN-VIVO

It is still uncertain whether multilineage hematopoietic progenitor ce lls are affected by human immunodeficiency virus-1 (HIV-1) infection i n vivo, The SCID-hu Thy/Liv model is permissive of long-term multiline age human hematopoiesis, including T lymphopoiesis. This model was use d to investigate the effects of HIV-1 infection on early hematopoietic progenitor function. We found that both lineage-restricted and multil ineage hematopoietic progenitors were depleted from grafts infected wi th either a molecular clone or a primary isolate of HIV-1. Depletion o f hematopoietic progenitors (including CD34(+) cells, colony-forming u nits in methylcellulose, and long-term culture-initiating cells) occur red several days before the onset of thymocyte depletion, indicating t hat the subsequent rapid decline in thymocyte numbers was due at least in part to loss of thymocyte progenitors. HIV-1 proviral genomes were not detected at high frequency in hematopoietic cells earlier than th e intrathymic T-progenitor cell stage, despite the depletion of such c ells in infected grafts. Proviral genomes were also not detected in co lonies derived from progenitor cells from infected grafts. These data demonstrate that HIV-1 infection interrupts both lineage-restricted an d multilineage hematopoiesis in vivo and suggest that depletion of ear ly hematopoietic progenitor cells occurs in the absence of direct vira l infection. (C) 1998 by The American Society of Hematology.