Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss - LAAS - Laboratoire d'Analyse et d'Architecture des Systèmes Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2018

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

Maeva Dupont
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Shariq Usmani
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Isabelle Gennero

Abstract

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.
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Dates and versions

hal-01764831 , version 1 (30-04-2018)

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Brigitte Raynaud-Messina, Lucie Bracq, Maeva Dupont, Shanti Souriant, Shariq Usmani, et al.. Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115 (11), pp.E2556 - E2565. ⟨10.1073/pnas.1713370115⟩. ⟨hal-01764831⟩
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