Impact of HIV Infection on Cellular Senescence and Potential Role in COPD Pathoge

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DESCRIPTION: COPD is one of the most prevalent comorbidities in HIV+ patients and is substantially more common in older HIV+ patients. An increasing number of studies have demonstrated a role of accelerated epithelial senescence in the development of COPD. Senescence can contribute to lung disease not only by impairing the ability of cells to repopulate an injured airway, but by secretion of inflammatory cytokine and growth factors, known as the "senescence-associated secretory phenotype (SASP). To date, a role of HIV infection in premature cellular senescence in the lung is unexplored. We hypothesize that HIV infection accelerates epithelial senescence, which ultimately predisposes to the premature development of COPD. To begin to address this question, we will examine whether bronchoalveolar lavage (BAL) from HIV+ patients is enriched with markers of SASP, and can induce senescence of primary lung epithelial cells compared to BAL from HIV- patients. In parallel, we will examine whether HIV-infected lymphocytes or macrophages induce lung epithelial senescence in vitro. These studies will fill gaps in our knowledge since very little is known about the consequences of HIV infection on the development of cellular senescence. These results will provide the foundation for future studies examining the contribution of cellular senescence to accelerated development of COPD in HIV+ patients.