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

doi:10.1128/JVI.75.22.10808-10814.2001

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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 circulatingcommitted progenitor cells. We now demonstrate that human cordblood-derived mast cell progenitors are susceptible to infectionwith macrophagetropic (M-tropic) and dualtropic human immunodeficiencyvirus 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 from4-week-old cultures of cord blood mononuclear cells maintainedin stem cell factor, interleukin-6 (IL-6), and IL-10 using a CD14depletion column. These progenitors expressed CCR3, CCR5, andCXCR4, as well as low levels of CD4. When infected in vitro withviruses pseudotyped with different HIV and simian immunodeficiencyvirus envelope glycoproteins, only M-tropic and dualtropic, butnot T-tropic, viruses were able to enter mast cell progenitors.Both the CCR5-specific monoclonal antibody 2D7 and TAK-779, anonpeptide inhibitor of CCR5-mediated viral entry, blocked HIV-1strain ADA infection by >80%. Cultures infected with replication-competentvirus produced progressively increasing amounts of virus for 21days as indicated by p24 antigen detection. Mast cell progenitorsthat were exposed to an M-tropic, green fluorescent protein-expressingHIV-1 strain exhibited fluorescence indicative of viral entryand replication on a single-cell level and retained virus productionduring differentiation. The trafficking of mast cell progenitorsto multiple tissues, combined with the long life span of maturemast cells, suggests that they could provide a widespread andpersistent HIV reservoir inAIDS.

^* Corresponding author. Mailing address: Division of Rheumatology, Immunology and Allergy, Brigham and Woman's Hospital, SmithBldg. 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.

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