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

While the survival rate of HIV-infected individuals has dramatically improved with the development of highly active anti-retroviral therapy, HIV-infected individuals have an increased risk for chronic disorders, including the development of COPD, manifesting as emphysema. The mechanisms of HIV-associated emphysema are not understood. Based on the knowledge that human airway basal cells (BC) function as stem/progenitor cells capable of differentiation into specialized ciliated and secretory cells during natural turnover and repair in response to injury, we hypothesized that HIV interacts with, and consequently induces pathologic programming of the BC that contributes to the development of emphysema. Overall design: Studies were designed to assess: (1) if HIV binds to, infects and/or replicates in BC; (2) identify which BC receptor(s) are responsible for HIV capture; and (3) the reprogramming of BC biology upon HIV exposure. Infectious HIVNL4-3 was used for all studies. Soluble heparan sulfate and heparinase III were used to prevent HIV/BC interactions. BC phenotypes after HIV exposure were assessed by TaqMan quantitative PCR, ELISA, phospho-MAPK array, protease array, cell invasion assay, and zymography.

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Chung NPY, Ou X, Khan KMF, Salit J, Kaner RJ, Crystal RG