Mechanism of Interaction Between Lung Surfactant Protein-D and Influenza A Virus Hemagglutinin

Abstract

Lung collectin surfactant proteins are pulmonary host defense proteins that contribute to innate, front-line defense against influenza A virus (IAV) and other inhaled pathogens. Collectins recognize viral glycans on the globular head of hemagglutinin (HA) on the IAV surface and initiate events leading to pathogen neutralization. Thus, effective pulmonary host defense requires fast recognition of IAV HA by collectins. In order to assist development of new approaches to collectin-based antiviral therapeutics, we investigated the mechanism underlying SP-D recognition of IAV HA using molecular dynamics simulations. Comparing the binding affinities of SP-Ds of human and swine on different IAV HA proteins, we showed that swine's SP-D has a higher binding affinity towards the glycans of HA proteins. In addition, starting from crystalized protein structures from X-ray diffraction experiments, our simulations identified the most stable docking configuration of the SP-D-HA complex, revealing how composition and location of glycans affect binding of SP-D to HA.