Through analysis of bone loss in HIV infection, a study uncovers a secondary viral target and potential viral reservoir in infected people. By some estimates, HIV-infected people are at six-fold heightened risk of bone mineral loss, compared with uninfected people. Antiretroviral drugs are tied to bone loss, but HIV can itself weaken bone by altering the balance between bone formation and resorption. Christel Verollet and colleagues tested whether HIV-1 directly targets osteoclasts, cells that secrete bone matrix-resorbing enzymes in a specialized scaffold called the sealing zone. The authors detected infected osteoclasts in femurs and tibias from HIV-1-infected mice and in cultures of human synovial joint membranes exposed to HIV-1. In laboratory dishes, the virus either directly infected osteoclasts or passed from infected T-helper cells, the main target, to osteoclasts through direct contact between the cells. Further, HIV-1 was found to replicate within osteoclasts with no cytotoxic effects, enhance the migration and adhesion of osteoclast precursors to bone, and increase the volume of resorbed bone. Enhanced bone resorption by osteoclasts mirrored enhanced activity of the Src enzyme, which helps form and stabilize sealing zones. The viral protein Nef, known to activate Src, boosted the activity of osteoclasts in vivo, potentially accelerating bone loss. According to the authors, osteoclasts represent little-explored targets of HIV-1 and may serve as putative viral reservoirs shielded from the reach of therapeutic drugs.
Article #17-13370: "Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss," by Brigitte Raynaud-Messina et al.
MEDIA CONTACT: Christel Verollet, The Institute of Pharmacology and Structural Biology, Toulouse, FRANCE; e-mail: <verollet@ipbs.fr>
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