Increased antiviral and opsonic activity of a highly multimerized collectin chimera.
Altering the carbohydrate binding properties of surfactant protein D (SP-D) [e.g., by replacing its carbohydrate recognition domain (CRD) with that of either mannose binding lectin (MBL) or conglutinin] can increase its activity against influenza A virus (IAV). The current study demonstrates that the degree of multimerization of SP-D is another independent determinant of antiviral activity. A chimeric collectin containing the N-terminus and collagen domain of human SP-D and the CRD of MBL formed high-molecular-weight multimers similar to those previously described for human SP-D. Using several complementary assays, and diverse viral strains, the chimeric multimers showed greater anti-IAV activity than similarly multimerized preparations of SP-D or incompletely oligomerized preparations of the chimera. More highly multimerized preparations of the chimera also caused greater increases in uptake of IAV by neutrophils. These studies may have implications for development of collectins as therapeutic agents and understanding of natural variations in susceptibility to IAV infection.
White
M R
MR
Department of Medicine, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, USA.
Crouch
E
E
Chang
D
D
Hartshorn
K L
KL
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry*; D002478:Cells, Cultured; D037222:Collectins; D006224:Cricetinae; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D009895:Opsonin Proteins / Q000494:pharmacology*; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D000998:Antiviral Agents; D002352:Carrier Proteins; D037222:Collectins; D006023:Glycoproteins; D009895:Opsonin Proteins; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins