Stemware... All About StemCell Stocks

[Preciouslife1]

Cell Host & Microbe, Volume 9, Issue 3, 223-234, 17 March 2011
Copyright © 2011 Elsevier Inc. All rights reserved.
10.1016/j.chom.2011.02.005

Referred to by: Profaning the Ultimate Sanctuary: HIV La...

Summary

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.
Authors
Christoph C. Carter, Lucy A. McNamara, Adewunmi Onafuwa-Nuga, Mark Shackleton, James Riddell, Dale Bixby, Michael R. Savona, Sean J. Morrison, Kathleen L. CollinsSee AffiliationsHint: Rollover Authors and Affiliations Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA
Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, USA
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA
Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109, USA
Corresponding author
These authors contributed equally to this work
Present address: Division of Hematology/Oncology and Bone Marrow Transplantation, San Antonio Military Medical Center; Department of Internal Medicine, University of Texas Health Science Center, San Antonio, TX 78236, USAHighlights
CXCR4-tropic HIV infects multipotent hematopoietic stem/progenitor cells (HSPCs)
CCR5-tropic HIV has minimal capacity to infect multipotent HSPCs
CXCR4-tropic HIV-infected human HSCs stably engraft in SCID mice
Chronic viremia is associated with a decline in bone marrow cell counts in vivo
...................................................................