Porcine Pulmonary Collectins Show Distinct Interactions with Influenza A Viruses: Role of the N-Linked Oligosaccharides in the Carbohydrate Recognition Domain~1

摘要

Influenza A virus (IAV) infections are a major cause of respiratory disease of humans and animals. Pigs can serve as important intermediate hosts for transmission of avian IAV strains to humans, and for the generation of reassortant strains; this may result in the appearance of new pandemic IAV strains in humans. We have studied the role of the porcine lung collectins surfactant proteins D and A (Psp-d and Psp-A), tow important components of the innate immune response against IAV. Hemagglutination inhibition assays revealed that both Psp-D and Psp-A display substantially greater inhibitory against IVA strains isolated from human, swine, and horse, than lung collectins form other animal species. The more potent activity of Psp-d, results from interactions mediated by the asparagines-linked oligosaccharide located in the carbohydrate recognition domain of Psp-d, which is absent in SP-Ds from other species characterized to date. Pressence of this sialylated oligosaccharide moiety enhances the anti-influenza activity of psp-d, as demonstrated by assays of viral aggregation, inhibition of infectivity, and neutrophil response to IAV. The greater hemagglutination inhibitory activity of psp-A is due to porcine-specific structural features of the conserved asparagines-linked oligosaccharide in the carbohydrate recognition domain of SP-A A more efficient lung collectin-mediated immune response against IAV in pigs may play a role in providing conditions by which pigs can act as "mixing vessel" hosts that can lead to the production of reassortant, pandemic strains of IAV.