HIV-1 utilizes the CXCR4 chemokine receptor to infect multipotent hematopoietic stem and progenitor cells

Christoph C. Carter, Lucy A. McNamara, Adewunmi Onafuwa-Nuga, Mark Shackleton, James Riddell IV, Dale Bixby, Michael R. Savona, Sean J. Morrison, Kathleen L. Collins

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72 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)223-234
Number of pages12
JournalCell Host & Microbe
Volume9
Issue number3
DOIs
Publication statusPublished - 17 Mar 2011
Externally publishedYes

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