Human immunodeficiency virus-1 infection interrupts thymopoiesis and multilineage hematopoiesis in vivo

Morgan Jenkins, Mary Beth Hanley, Mary Beth Moreno, Eric Wieder, Joseph M. McCune

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82 Scopus citations

Abstract

It is still uncertain whether multilineage hematopoietic progenitor cells are affected by human immunodeficiency virus-1 (HIV-1) infection in vivo. The SCID-hu Thy/Liv model is permissive of long-term multilineage human hematopoiesis, including T lymphopoiesis. This model was used to investigate the effects of HIV-1 infection on early hematopoietic progenitor function. We found that both lineage-restricted and multilineage hematopoietic progenitors were depleted from grafts infected with either a molecular clone or a primary isolate of HIV-1. Depletion of hematopoietic progenitors (including CD34+ cells, colony-forming units in methyl-cellulose, and long-term culture- initiating cells) occurred several days before the onset of thymocyte depletion, indicating that 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 the intrathynic T-progenitor cell stage, despite the depletion of such cells in infected grafts. Proviral genomes were also not detected in colonies derived from progenitor cells from infected grafts. These data demonstrate the HIV-1 infection interrupts both lineage-restricted and multilineage hematopoiesis in vivo and suggest that depletion of early hematopoietic progenitor cells occurs in the absence of direct viral infection.

Original languageEnglish (US)
Pages (from-to)2672-2678
Number of pages7
JournalBlood
Volume91
Issue number8
StatePublished - Apr 15 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Jenkins, M., Hanley, M. B., Moreno, M. B., Wieder, E., & McCune, J. M. (1998). Human immunodeficiency virus-1 infection interrupts thymopoiesis and multilineage hematopoiesis in vivo. Blood, 91(8), 2672-2678.