Title | HIV-1 infection of hematopoietic progenitor cells in vivo in humanized mice. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Nixon CC, Vatakis DN, Reichelderfer SN, Dixit D, Kim SG, Uittenbogaart CH, Zack JA |
Journal | Blood |
Volume | 122 |
Issue | 13 |
Pagination | 2195-204 |
Date Published | 2013 Sep 26 |
ISSN | 1528-0020 |
Keywords | Animals, Disease Models, Animal, DNA, Viral, Flow Cytometry, Hematopoiesis, Hematopoietic Stem Cells, HIV Infections, HIV-1, Humans, Mice, Real-Time Polymerase Chain Reaction |
Abstract | HIV infection has been associated with defective hematopoiesis since the earliest days of the HIV/AIDS epidemic. Generation of all hematopoietic lineages suffers in the face of infection. The mechanisms by which HIV impairs normal blood cell development remain unclear, and direct infection of intermediate hematopoietic progenitors has not been established as a source of HIV-associated hematopoietic pathology. Here, we demonstrate infection of multiple subsets of highly purified intermediate hematopoietic progenitors by wild-type HIV both in vitro and in vivo. Although direct infection is clearly cytotoxic, we find that some infected progenitors can survive and harbor proviral DNA. We report intermediate hematopoietic progenitors to be a novel target of infection and their permissivity to infection increases with development. Further, the nonobese diabetic severe combined immunodeficiency common γ chain knockout-bone marrow-liver-thymus humanized mouse provides a unique model for studying the impact of HIV infection on bone marrow-based human hematopoiesis. |
DOI | 10.1182/blood-2013-04-496950 |
Alternate Journal | Blood |
PubMed ID | 23886835 |
PubMed Central ID | PMC3785119 |
Grant List | R21DA031036-01A1 / DA / NIDA NIH HHS / United States R01 AI070010 / AI / NIAID NIH HHS / United States T32AI060567 / AI / NIAID NIH HHS / United States R01AI103385 / AI / NIAID NIH HHS / United States R21 DA031036 / DA / NIDA NIH HHS / United States P30 AI028697 / AI / NIAID NIH HHS / United States R01 AI103385 / AI / NIAID NIH HHS / United States AI028697 / AI / NIAID NIH HHS / United States R01AI070010 / AI / NIAID NIH HHS / United States T32 AI060567 / AI / NIAID NIH HHS / United States U19 AI096113 / AI / NIAID NIH HHS / United States |
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