Mechanism of binding of surfactant protein D to influenza A viruses: importance of binding to haemagglutinin to antiviral activity.
Collectins are important in the initial containment of a variety of pathogens, including influenza A virus (IAV). We provide the first systematic evaluation of the oligosaccharide-binding sites for pulmonary surfactant protein D (SP-D) on specific IAV coat glycoproteins and define the relationship between this binding and antiviral activity. With the use of several techniques, SP-D was found to bind via its carbohydrate-recognition domain (CRD) to mannosylated, N-linked carbohydrates on the HA(1) domain of the haemagglutinin (HA) and on the neuraminidase of IAV. Using a set of IAV strains that differed in the level and site of glycosylation, and a panel of recombinant collectins, we found that binding of SP-D to the globular domain of the HA was critical in mediating the inhibition of viral haemagglutination activity and infectivity. We also demonstrated that the pattern of binding of a collectin to IAV glycoproteins can be modified by altering the monosaccharide-binding affinity of its CRD or by linking the CRD to a different N-terminal/collagen domain. These studies clarify the mechanisms of viral neutralization by collectins and might be useful in engineering collectins for enhanced antiviral activity.
Hartshorn
K L
KL
Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA. khartsho@bu.edu
White
M R
MR
Voelker
D R
DR
Coburn
J
J
Zaner
K
K
Crouch
E C
EC
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002213:Capsid / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002417:Cattle; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006388:Hemagglutinins / Q000378:metabolism*; D009980:Influenza A virus / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D018076:DNA, Complementary; D006023:Glycoproteins; D006388:Hemagglutinins; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D009439:Neuraminidase; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase