Intrinsic Human Immunodeficiency Virus Type 1 Resistance of Hematopoietic Stem Cells Despite Coreceptor Expression

Hongmei Shen; Tao Cheng; Frederick I Preffer; David Dombkowski; Michael H Tomasson; David E Golan; Otto Yang; Wolfgang Hofmann; Joseph G Sodroski; Andrew D Luster; David T Scadden

doi:10.1128/JVI.73.1.728-737.1999

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Intrinsic Human Immunodeficiency Virus Type 1 Resistance of Hematopoietic Stem Cells Despite Coreceptor Expression

Journal article

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Intrinsic Human Immunodeficiency Virus Type 1 Resistance of Hematopoietic Stem Cells Despite Coreceptor Expression

Hongmei Shen, Tao Cheng, Frederick I Preffer, David Dombkowski, Michael H Tomasson, David E Golan, Otto Yang, Wolfgang Hofmann, Joseph G Sodroski, Andrew D Luster, …

Journal of virology, Vol.73(1), pp.728-737

01/1999

DOI: 10.1128/JVI.73.1.728-737.1999

PMCID: PMC103880

PMID: 9847379

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Abstract

Interactions of human immunodeficiency virus type 1 (HIV-1) with hematopoietic stem cells may define restrictions on immune reconstitution following effective antiretroviral therapy and affect stem cell gene therapy strategies for AIDS. In the present study, we demonstrated mRNA and cell surface expression of HIV-1 receptors CD4 and the chemokine receptors CCR-5 and CXCR-4 in fractionated cells representing multiple stages of hematopoietic development. Chemokine receptor function was documented in subsets of cells by calcium flux in response to a cognate ligand. Productive infection by HIV-1 via these receptors was observed with the notable exception of stem cells, in which case the presence of CD4, CXCR-4, and CCR-5, as documented by single-cell analysis for expression and function, was insufficient for infection. Neither productive infection, transgene expression, nor virus entry was detectable following exposure of stem cells to either wild-type HIV-1 or lentivirus constructs pseudotyped in HIV-1 envelopes of macrophage-tropic, T-cell-tropic, or dualtropic specificity. Successful entry into stem cells of a vesicular stomatitis virus G protein-pseudotyped HIV-1 construct demonstrated that the resistance to HIV-1 was mediated at the level of virus-cell membrane fusion and entry. These data define the hematopoietic stem cell as a sanctuary cell which is resistant to HIV-1 infection by a mechanism independent of receptor and coreceptor expression that suggests a novel means of cellular protection from HIV-1.

Virus-Cell Interactions

Details

Title: Subtitle: Intrinsic Human Immunodeficiency Virus Type 1 Resistance of Hematopoietic Stem Cells Despite Coreceptor Expression
Creators: Hongmei Shen - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
Tao Cheng - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
Frederick I Preffer - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
David Dombkowski - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
Michael H Tomasson - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
David E Golan - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
Otto Yang - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
Wolfgang Hofmann - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
Joseph G Sodroski - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
Andrew D Luster - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
David T Scadden - AIDS Research Center, MGH Cancer Center, Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Department of Medicine
Resource Type: Journal article
Publication Details: Journal of virology, Vol.73(1), pp.728-737
Publisher: American Society for Microbiology
DOI: 10.1128/JVI.73.1.728-737.1999
PMID: 9847379
PMCID: PMC103880
ISSN: 0022-538X
eISSN: 1098-5514
Language: English
Date published: 01/1999
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094774502771

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