Macrophage-derived HIV-1 carries bioactive TGF-beta

Infected T cells and macrophages are the main producers of HIV-1 in infected individuals. Upon release from infected cells, HIV-1 incorporates various cellular membrane proteins, some of which are specific for these cells. However, the functions of cell-encoded proteins in virions remain largely unknown. We performed flow virometry to identify, in plasma of HIV-infected individuals, macrophage- and T-cell-derived HIV-1 virions, using cell-specific markers CD36 and CD27, respectively. Using four different methods, we demonstrated that CD36 on virions binds the immunosuppressive cytokine transforming growth factor beta (TGF-β) through a ligand, thrombospondin one (TSP-1). Flow virometry of individual virions showed that TGF-β was present on CD36+ virions (average, 28.2% ± 6.6% (n = 3)) but not on CD27+ virions (average, 1% ± 0.1% (n = 3)). TGF-β molecules present on captured CD36+ virions were biologically active, as evaluated with a reporter cell line. Delivery of TGF-β on HIV virions to HIV target cells may affect them, playing a significant role in viral pathogenesis.