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Journal of Virology, November 2001, p. 10808-10814, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.10808-10814.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human Mast Cell Progenitors Can Be Infected by Macrophagetropic Human Immunodeficiency Virus Type 1 and Retain Virus with Maturation In Vitro

Norbert Bannert,1,2 Michael Farzan,1 Daniel S. Friend,2,3,4 Hiroshi Ochi,4 Kursteen S. Price,3,4 Joseph Sodroski,1,2,5 and Joshua A. Boyce3,4,6,7,*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute,1 Departments of Pathology,2 Medicine,3 and Pediatrics,6 Harvard Medical School, Department of Immunology and Infectious Diseases, Harvard School of Public Health,5 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital,4 and Partner's Asthma Center,7 Boston, Massachusetts

Received 21 May 2001/Accepted 1 August 2001

Mast cells are critical components of innate and adaptive immunity that differentiate in tissues in situ from circulating committed progenitor cells. We now demonstrate that human cord blood-derived mast cell progenitors are susceptible to infection with macrophagetropic (M-tropic) and dualtropic human immunodeficiency virus type 1 (HIV-1) isolates but not with T-cell-tropic (T-tropic) strains. Mast cell progenitors (c-kit+ CD13+ cells with chloroacetate esterase activity) were purified from 4-week-old cultures of cord blood mononuclear cells maintained in stem cell factor, interleukin-6 (IL-6), and IL-10 using a CD14 depletion column. These progenitors expressed CCR3, CCR5, and CXCR4, as well as low levels of CD4. When infected in vitro with viruses pseudotyped with different HIV and simian immunodeficiency virus envelope glycoproteins, only M-tropic and dualtropic, but not T-tropic, viruses were able to enter mast cell progenitors. Both the CCR5-specific monoclonal antibody 2D7 and TAK-779, a nonpeptide inhibitor of CCR5-mediated viral entry, blocked HIV-1 strain ADA infection by >80%. Cultures infected with replication-competent virus produced progressively increasing amounts of virus for 21 days as indicated by p24 antigen detection. Mast cell progenitors that were exposed to an M-tropic, green fluorescent protein-expressing HIV-1 strain exhibited fluorescence indicative of viral entry and replication on a single-cell level and retained virus production during differentiation. The trafficking of mast cell progenitors to multiple tissues, combined with the long life span of mature mast cells, suggests that they could provide a widespread and persistent HIV reservoir in AIDS.

* Corresponding author. Mailing address: Division of Rheumatology, Immunology and Allergy, Brigham and Woman's Hospital, Smith Bldg. Rm. 618, 1 Jimmy Fund Way, Boston, MA 02115. Phone: (617) 525-1233. Fax: (617) 525-1310. E-mail: Jboyce{at}rics.bwh.harvard.edu.

Journal of Virology, November 2001, p. 10808-10814, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.10808-10814.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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