HIV viral protein expression disrupts bone tissue homeostasis in mice

HIV infection is associated with metabolic and skeletal comorbidities that persist despite effective antiretroviral therapy. However, the direct contribution of viral proteins to these alterations remains incompletely understood. Here, we investigated the impact of HIV transgene expression on adipose tissue content, inflammatory status, and bone tissue homeostasis in mice. HIV transgenic mice Tg26 exhibited lipoatrophy in both young and aged animals, accompanied by only mild changes in systemic inflammatory parameters. In parallel, HIV transgene expression was associated with early-onset bone loss, affecting both cortical and trabecular compartments. Molecular analyses of calvarial bone revealed dysregulation of key regulators of bone remodeling, indicating an imbalance in osteoblast and osteoclast activity. Consistently, circulating bone turnover markers were elevated in HIV transgenic mice, supporting a state of increased, coupled high-turnover bone remodeling. Collectively, these findings suggest that HIV viral protein expression is sufficient to induce persistent alterations in skeletal homeostasis, highlighting a role of viral factors in the pathogenesis of HIV-associated metabolic and bone disease.