HIV-1 Utilizes the CXCR4 Chemokine Receptor to Infect Multipotent Hematopoietic Stem and Progenitor Cells

Cell Host Microbe. 2011 Mar 17;9(3):223-234. doi: 10.1016/j.chom.2011.02.005.

Abstract

HIV infection is characterized by gradual immune system collapse and hematopoietic dysfunction. We recently showed that HIV enters multipotent hematopoietic progenitor cells and establishes both active cytotoxic and latent infections that can be reactivated by myeloid differentiation. However, whether these multipotent progenitors include long-lived hematopoietic stem cells (HSCs) that could establish viral reservoirs for the life of the infected person remains unknown. Here we provide direct evidence that HIV targets long-lived HSCs and show that infected HSCs yield stable, multilineage engraftment in a xenograft model. Furthermore, we establish that the capacity to use the chemokine receptor CXCR4 for entry determines whether a virus will enter multipotent versus differentiated progenitor cells. Because HSCs live for the life span of the infected person and are crucial for hematopoietic health, these data may explain the poor prognosis associated with CXCR4-tropic HIV infection and suggest HSCs as long-lived cellular reservoirs of latent HIV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / metabolism
  • CD4 Antigens / metabolism
  • Cell Count
  • Cells, Cultured
  • Cloning, Molecular
  • Glycoproteins / metabolism
  • Green Fluorescent Proteins / biosynthesis
  • HIV Infections / pathology*
  • HIV-1 / genetics
  • HIV-1 / pathogenicity
  • HIV-1 / physiology*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Hematopoietic Stem Cells / virology*
  • Host-Pathogen Interactions
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Peptides / metabolism
  • Receptors, CXCR4 / metabolism*
  • Recombinant Proteins / biosynthesis
  • Transplantation, Heterologous
  • Viral Load
  • Viral Plaque Assay
  • Viral Tropism
  • Virus Latency

Substances

  • AC133 Antigen
  • Antigens, CD
  • CD4 Antigens
  • CXCR4 protein, human
  • Glycoproteins
  • Peptides
  • Receptors, CXCR4
  • Recombinant Proteins
  • Green Fluorescent Proteins