HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype

While highly active anti-retroviral therapy has dramatically improved the survival of HIV-infected individuals, there is an increased risk for other co-morbidities, such as COPD, manifesting as emphysema. Given that emphysema originates around the airways and that human airway basal cells (BCs) are adult airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a distinct phenotype that contributes to the development of emphysema. Our data indicate that HIV binds to but does not replicate in BCs. HIV binding to BCs induces them to acquire an invasive phenotype, mediated by upregulation of MMP-9 expression through activation of MAPK signaling pathways. This HIV-induced "destructive" phenotype may contribute to degradation of extracellular matrix and tissue damage relevant to the development of emphysema commonly seen in HIV⁺ individuals.