UBC Theses and Dissertations
The airway epithelial response to human immunodeficiency virus : implications for HIV-associated chronic obstructive pulmonary disease Hansi, Ravneet Kaur
RATIONALE: Despite the reduction in HIV-related mortality since the introduction of antiretroviral therapy, people living with HIV (PLWH) face a higher risk of developing age-associated comorbidities such as chronic obstructive pulmonary disease (COPD). Studies have found that HIV and COPD are independently associated with increased susceptibility and worse manifestations from respiratory viral infections. We hypothesize that COPD in PLWH is marked by increased inflammation in the airway epithelium which may potentiate injury during respiratory viral infections. METHODS: Primary human bronchial epithelial cells obtained from control, COPD, HIV, and HIV/COPD donors were cultured as monolayers and air-liquid interfaces (ALIs). RNA and protein lysates from these cultures were used to quantify HIV receptor mRNA and protein expression via qRT-PCR and western blot, respectively. ALI cultures were infected with respiratory syncytial virus (RSV) for 90 minutes and transepithelial electrical resistance (TEER) values were taken at time points: 0h, 24h, 48h and 72h. ALI cultures underwent immunohistochemistry staining for E-Cadherin quantification and mucus production quantification through Periodic Acid Schiff and MUC5AC staining. RESULTS: Western blot analysis of monolayer lysates demonstrated increased expression of CXCR4 in PLWH with and without COPD and increased expression of CCR5 in PLWH with COPD compared to control individuals. There was a trend towards higher CD4 expression in PLWH with and without COPD compared to control individuals. However, these differences were not found in either protein or mRNA HIV receptor expression in ALIs. TEER data demonstrated a decrease in epithelial resistance in RSV-infected ALIs derived from COPD and PLWH with COPD compared to PLWH without COPD and control individuals. There were no significant differences seen in E-cadherin expression and mucus production in RSV-infected ALIs. CONCLUSION: With an increased expression of HIV canonical receptors in the basal epithelial layer, particularly CCR5 and CXCR4, in PLWH with COPD, a greater interaction between virus and the airway epithelium may be possible, potentially causing damage to the airway epithelium. Furthermore, RSV infection induces greater epithelial permeability in patients with COPD regardless of HIV status. This could indicate that post-viral small airway injury may be driven more by COPD status rather than HIV infection alone.
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