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A3850 - Pulmonary Surfactant Lipids Antagonize Human Rhinovirus Infection
Author Block: M. Numata-Nakamura1, Y. A. Bochkov2, M. A. Seibold3, J. Everman4, H. Lee5, D. R. Voelker6; 1Medicine, National Jewish Health, Tokyo Metropolitan Bokutoh Hospital, Denver, Japan, CO, United States, 2University of Wisconsin-Madison, Madison, WI, United States, 3Integrated Center for Genes, Enviroment and Health, National Jewish Health, Denver, CO, United States, 4National Jewish Health, Denver, CO, United States, 5Medicine, National Jewish Health, Tokyo Bokutoh Metropolitan Hospital, Denver, CO, United States, 6Medicine, National Jewish Health, Denver, CO, United States.
Background: Human Rhinoviruses (HRVs) are major instigators of acute exacerbations of COPD and asthma. Epidemiologic studies show the HRV-C subtype is associated with more severe illness and hospitalizations of patients with chronic lung disease. Unlike other HRVs, HRV-C uses a novel receptor, CDHR3, to infect epithelial cells. Pulmonary surfactant is an extracellular complex of lipids and proteins that plays a central role in regulating innate immunity in the lung. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG), and phosphatidylinositol (PI), are potent regulators of inflammatory processes, and exert anti-viral activity against respiraroty syncyntitial virus (RSV) and Influenza A virus.
Objective: The primary objective of this study was to examine and quantify POPG and PI potency against HRV-C, using normal human bronchial epithelial (NHBE) cells, and bronchial epithelial cells from COPD subjects, and nasal epithelial (HNEC) cells obtained from control and COPD subjects. These cells were grown in ALI cultures to maintain differentiation.
Methods: To examine our hypothesis, we measured the protective effects of POPG and PI against HRVC-15-GFP infection and inflammation using differentiated bronchial epithelial cells from normal and COPD subjects and nasal epithelial cells derived from normal subjects. Viral replication and anti-viral gene expression was quantified by qRT-PCR. Viral infection was measured by quantifying fluorescent viral foci.
Results: PI inhibited HRVC15-replication in NHBE by 95%, as assessed by qRT-PCR. Microscopy showed fluorescent foci (FFU), were reduced by a factor of 102. PI also inhibited anti-viral gene expression (IFN-λ, IRF-7, MDA-5) elicited by HRVC-15-GFP infection. In bronchial epithelial cells from COPD subjects, PI reduced HRVC15-GFP replication by 94%, and FFU values by a factor of 20; but there were no significant changes in anti-viral gene expression. POPG and PI also reduced HRVC-15 replication by 95% in HNEC as quantified by qRT-PCR.
Conclusions: POPG and PI were highly protective against HRVC-15 infection in vitro. These findings suggest that intranasal administration, or inhalation of POPG, or PI, may be an effective new approach for treating acute exacerbations of respiratory diseases caused by HRVC infection.