Macrophage-derived HIV-1 carries bioactive TGF-beta

Sci Rep. 2019 Dec 13;9(1):19100. doi: 10.1038/s41598-019-55615-8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD36 Antigens / metabolism
  • Cell Membrane / metabolism
  • Cytokines / metabolism
  • HIV Infections / metabolism
  • HIV-1 / metabolism*
  • Humans
  • Immunohistochemistry
  • Inflammation
  • Ligands
  • Macrophages / virology*
  • Mice
  • NIH 3T3 Cells
  • RNA, Viral / metabolism
  • Thrombospondin 1 / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Viral Load
  • Virion / metabolism

Substances

  • CD36 Antigens
  • Cytokines
  • Ligands
  • RNA, Viral
  • TGFB1 protein, human
  • Tgfb1 protein, mouse
  • Thrombospondin 1
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor Receptor Superfamily, Member 7