Human mast cell progenitors can be infected by macrophagetropic human immunodeficiency virus type 1 and retain virus with maturation in vitro

Mast cells are critical components of innate and adaptive immunity that dif ferentiate 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 hu man immunodeficiency virus type 1 (HIV-1) isolates but not with T-cell-trop ic (T-tropic) strains. Mast cell progenitors (c-kit(+) CD13(+) cells with c hloroacetate esterase activity) were purified from 4-week-old cultures of c ord 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 vitr o with viruses pseudotyped with different HIV and simian immunodeficiency v irus 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-mediate d viral entry, blocked HIV-1 strain ADA infection by > 80%. Cultures infect ed with replication-competent virus produced progressively increasing amoun ts of virus for 21 days as indicated by p24 antigen detection. Mast cell pr ogenitors that were exposed to an M-tropic, green fluorescent protein-expre ssing HIV-1 strain exhibited fluorescence indicative of viral entry and rep lication on a single-cell level and retained virus production during differ entiation. The trafficking of mast cell progenitors to multiple tissues, co mbined with the long life span of mature mast cells, suggests that they cou ld provide a widespread and persistent HIV reservoir in AIDS.