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We decipher the cellular mechanisms by which HIV-1 contributes to enhanced bone degradation in human osteoclasts, showing that the virus modifies the structure and function of the sealing zone, the bone resorption machinery of osteoclasts. We identify the viral protein Nef as the key factor responsible for such effects. As a proof-of-concept, we correlate bone deficit in transgenic Nef-expressing mice with enhanced osteoclast activity. Therefore, our findings provide formal evidence that osteoclasts constitute HIV-1 host target cells, contributing to bone deficits in vivo.<\/jats:p>","DOI":"10.1073\/pnas.1713370115","type":"journal-article","created":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T14:33:25Z","timestamp":1519137205000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":66,"title":["Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss"],"prefix":"10.1073","volume":"115","author":[{"given":"Brigitte","family":"Raynaud-Messina","sequence":"first","affiliation":[{"name":"Institut de Pharmacologie et de Biologie Structurale, Universit\u00e9 de Toulouse, CNRS, Universit\u00e9 Paul Sabatier, 31400 Toulouse Cedex 4, France;"},{"name":"International Associated Laboratory, CNRS \u201cImmuno-Metabolism-Macrophages-Tuberculosis\/HIV\u201d (1167), 31000 Toulouse, France;"},{"name":"International Associated Laboratory, CNRS 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