Porcine pulmonary collectins show distinct interactions with influenza A viruses: role of the N-linked oligosaccharides in the carbohydrate recognition domain.
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), two important components of the innate immune response against IAV. Hemagglutination inhibition assays revealed that both pSP-D and pSP-A display substantially greater inhibitory activity against IAV strains isolated from human, swine, and horse, than lung collectins from other animal species. The more potent activity of pSP-D results from interactions mediated by the asparagine-linked oligosaccharide located in the carbohydrate recognition domain of pSP-D, which is absent in SP-Ds from other species characterized to date. Presence 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 asparagine-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.
van Eijk
Martin
M
Departments of Biochemistry and Cell Biology, Graduate School of Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. m.vaneijk@vet.uu.nl
White
Mitchell R
MR
Crouch
Erika C
EC
Batenburg
Joseph J
JJ
Vaandrager
Arie B
AB
Van Golde
Lambert M G
LM
Haagsman
Henk P
HP
Hartshorn
Kevan L
KL
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000821:virology; D002236:Carbohydrate Conformation; D015536:Down-Regulation / Q000502:physiology; D006031:Glycosylation; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000378:metabolism / Q000517:prevention & control / Q000821:virology; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000502:physiology* / Q000821:virology*; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine
D000998:Antiviral Agents; D009844:Oligosaccharides; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins