A unique sugar-binding site mediates the distinct anti-influenza activity of pig surfactant protein D.
Pigs can act as intermediate hosts by which reassorted influenza A virus (IAV) strains can be transmitted to humans and cause pandemic influenza outbreaks. The innate host defense component surfactant protein D (SP-D) interacts with glycans on the hemagglutinin of IAV and contributes to protection against IAV infection in mammals. This study shows that a recombinant trimeric neck lectin fragment derived from porcine SP-D (pSP-D) exhibits profound inhibitory activity against IAV, in contrast to comparable fragments derived from human SP-D. Crystallographic analysis of the pSP-D fragment complexed with a viral sugar component shows that a unique tripeptide loop alters the lectin site conformation of pSP-D. Molecular dynamics simulations highlight the role of this flexible loop, which adopts a more stable conformation upon sugar binding and may facilitate binding to viral glycans through contact with distal portions of the branched mannoside. The combined data demonstrate that porcine-specific structural features of SP-D contribute significantly to its distinct anti-IAV activity. These findings could help explain why pigs serve as important reservoirs for newly emerging pathogenic IAV strains.
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
Martin
M
van Eijk
Michael J
MJ
Rynkiewicz
Mitchell R
MR
White
Kevan L
KL
Hartshorn
Xueqing
X
Zou
Klaus
K
Schulten
Dong
D
Luo
Erika C
EC
Crouch
Tanya R
TR
Cafarella
James F
JF
Head
Henk P
HP
Haagsman
Barbara A
BA
Seaton
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002478:Cells, Cultured; D003460:Crystallization; D017931:DNA Primers; D004285:Dogs; D009980:Influenza A virus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016297:Mutagenesis, Site-Directed; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D013552:Swine
D000998:Antiviral Agents; D017931:DNA Primers; D037663:Pulmonary Surfactant-Associated Protein D