Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss

Proc Natl Acad Sci U S A. 2018 Mar 13;115(11):E2556-E2565. doi: 10.1073/pnas.1713370115. Epub 2018 Feb 20.


Bone deficits are frequent in HIV-1-infected patients. We report here that osteoclasts, the cells specialized in bone resorption, are infected by HIV-1 in vivo in humanized mice and ex vivo in human joint biopsies. In vitro, infection of human osteoclasts occurs at different stages of osteoclastogenesis via cell-free viruses and, more efficiently, by transfer from infected T cells. HIV-1 infection markedly enhances adhesion and osteolytic activity of human osteoclasts by modifying the structure and function of the sealing zone, the osteoclast-specific bone degradation machinery. Indeed, the sealing zone is broader due to F-actin enrichment of its basal units (i.e., the podosomes). The viral protein Nef is involved in all HIV-1-induced effects partly through the activation of Src, a regulator of podosomes and of their assembly as a sealing zone. Supporting these results, Nef-transgenic mice exhibit an increased osteoclast density and bone defects, and osteoclasts derived from these animals display high osteolytic activity. Altogether, our study evidences osteoclasts as host cells for HIV-1 and their pathological contribution to bone disorders induced by this virus, in part via Nef.

Keywords: HIV-1 infection; Nef; bone loss; osteoclast; podosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Bone Resorption / etiology*
  • Bone Resorption / metabolism
  • Bone Resorption / pathology
  • Bone Resorption / physiopathology
  • Bone and Bones / metabolism
  • Cell Adhesion
  • Female
  • HIV Infections / complications*
  • HIV Infections / metabolism
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Mice
  • Osteoclasts / cytology
  • Osteoclasts / metabolism
  • Osteoclasts / virology*
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / metabolism


  • Actins
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1