Critical role for cross-linking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus.
Collectins are multimeric host defence lectins with trimeric CRDs (carbohydrate-recognition domains) and collagen and N-terminal domains that form higher-order structures composed of four or more trimers. Recombinant trimers composed of only the CRD and adjacent neck domain (termed NCRD) retain binding activity for some ligands and mediate some functional activities. The lung collectin SP-D (surfactant protein D) has strong neutralizing activity for IAVs (influenza A viruses) in vitro and in vivo, however, the NCRD derived from SP-D has weak viral-binding ability and lacks neutralizing activity. Using a panel of mAbs (monoclonal antibodies) directed against the NCRD in the present study we show that mAbs binding near the lectin site inhibit antiviral activity of full-length SP-D, but mAbs which bind other sites on the CRD do not. Two of the non-blocking mAbs significantly increased binding and antiviral activity of NCRDs as assessed by haemagglutination and neuraminidase inhibition and by viral neutralization. mAb-mediated cross-linking also enabled NCRDs to induce viral aggregation and to increase viral uptake by neutrophils and virus-induced respiratory burst responses by these cells. These results show that antiviral activities of SP-D can be reproduced without the N-terminal and collagen domains and that cross-linking of NCRDs is essential for antiviral activity of SP-D with respect to IAV.
Tecle
Tesfaldet
T
Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
White
Mitchell R
MR
Sorensen
Grith
G
Gantz
Donald
D
Kacak
Nilgun
N
Holmskov
Uffe
U
Smith
Kelly
K
Crouch
Erika C
EC
Hartshorn
Kevan L
KL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D037102:Lectins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000821:virology; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D016897:Respiratory Burst; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D037102:Lectins; D037663:Pulmonary Surfactant-Associated Protein D; D014764:Viral Proteins; D009439:Neuraminidase