Investigating the Interaction of SP-A and SP-D with Respiratory Syncytial Virus in Human Bronchial Epithelial Cells.

 Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization of infants in developed countries. Surfactant proteins A and D (SP-A and SP-D) are important innate immune molecules expressed throughout the human respiratory tract and present in pulmonary surfactant which covers the alveolar epithelium. Through binding carbohydrates on the surface of pathogens, they enhance their neutralization, agglutination and clearance. They also modulate the lung inflammatory immune response. Previous reports in SP-A and SP-D deficient mice have suggested their importance in promoting clearance of RSV from the murine respiratory tract.

 The aim of this work was to characterize the interaction of SP-A and SP-D with RSV in a human model and their capacity to prevent infection of immortalized human bronchial epithelial cells (AALEB) by an established clinical strain of RSV-A.

 RSV infection and replication was determined using RT-qPCR. Pre-incubation of RSV with both SP-A and SP-D reduced levels of infection of AALEB cells in a dose-dependent manner. Pre-incubation with 10μg/ml of SP-A decreased RSV infection by 57.8% (n=3, P<0.01). Pre-incubation with 10μg/ml of SP-D decreased RSV infection by 53.7% (n=3, P<0.01). The capacity of SP-A and SP-D to bind RSV fusion (F) protein has been evaluated by surface plasmon resonance and ELISA.

 We have shown in this human model that both SP-A and SP-D can directly prevent infection of human AALEB cells with RSV A. We speculate that our recombinant versions of SP-A and SP-D may have therapeutic potential and protect susceptible infants to RSV infection.