Brigitte Raynaud
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Project: Osteoclasts are HIV-1 host cells: contribution to virus-induced bone disorders
Bone defects have long been described in HIV-infected patients. There is now evidence showing that the virus, via the dysregulation of the immune system, is involved in altered bone homeostasis. Because osteoclasts share a common myeloid origin with macrophages that are main HIV-1 targets, we hypothesize that the virus could also infect these cells. We have shown that HIV-1 enters and replicates in osteoclasts and in their precursors, using human monocyte-derived osteoclasts in vitro and osteoclasts present in synovial tissues. HIV infection enhanced pre-osteoclast mesenchymal migration ability and also osteoclast differentiation and resorption activity. These HIV-mediated effects were linked to modifications in the size and F-actin density of the sealing zone, the osteoclast-specific podosome structure essential for bone attachment and activity. The viral protein Nef was necessary for all these effects, in part through activation of Src. Our results suggest that HIV infection of mature osteoclasts or their precursors, through function of Nef, participates in bone disorders observed in HIV patients.
Bone defects have long been described in HIV-infected patients. There is now evidence showing that the virus, via the dysregulation of the immune system, is involved in altered bone homeostasis. Because osteoclasts share a common myeloid origin with macrophages that are main HIV-1 targets, we hypothesize that the virus could also infect these cells. We have shown that HIV-1 enters and replicates in osteoclasts and in their precursors, using human monocyte-derived osteoclasts in vitro and osteoclasts present in synovial tissues. HIV infection enhanced pre-osteoclast mesenchymal migration ability and also osteoclast differentiation and resorption activity. These HIV-mediated effects were linked to modifications in the size and F-actin density of the sealing zone, the osteoclast-specific podosome structure essential for bone attachment and activity. The viral protein Nef was necessary for all these effects, in part through activation of Src. Our results suggest that HIV infection of mature osteoclasts or their precursors, through function of Nef, participates in bone disorders observed in HIV patients.
Animal and Cellular models:
- Culture of osteoclasts and macrophages derived from human CD14+ monocytes
- Culture of human synovial explants
Techniques and Methods:
- cell biology technics, bone resorption assay, 3D migration assay, adhesion assay