Enhanced anti-influenza activity of a surfactant protein D and serum conglutinin fusion protein.
We previously demonstrated that bovine serum conglutinin has markedly greater ability to inhibit influenza A virus (IAV) infectivity than other collectins. We now show that recombinant conglutinin and a chimeric protein containing the NH(2) terminus and collagen domain of rat pulmonary surfactant protein D (rSP-D) fused to the neck region and carbohydrate recognition domain (CRD) of conglutinin (termed SP-D/Cong(neck+CRD)) have markedly greater ability to inhibit infectivity of IAV than wild-type recombinant rSP-D, confirming that the potent IAV-neutralizing activity of conglutinin resides in its neck region and CRD. Furthermore, by virtue of incorporation of the NH(2) terminus and collagen domain of SP-D, SP-D/Cong(neck+CRD) caused substantially greater aggregation of IAV particles and enhancement of neutrophil binding of, and H(2)O(2) responses to, IAV than recombinant conglutinin or recombinant rSP-D. Hence, SP-D/Cong(neck+CRD) combined favorable antiviral and opsonic properties of conglutinin and SP-D. This study demonstrates an association of specific structural domains of SP-D and conglutinin with specific functional properties and illustrates that antimicrobial activities of wild-type collectins can be enhanced through recombinant strategies.
Hartshorn
K L
KL
Departments of Medicine and Pathology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. khartsho@bu.edu
Sastry
K N
KN
Chang
D
D
White
M R
MR
Crouch
E C
EC
D000818:Animals; D002417:Cattle; D002678:Chimera; D037222:Collectins; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006384:Hemagglutination / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009980:Influenza A virus / Q000378:metabolism / Q000502:physiology; D007251:Influenza, Human / Q000517:prevention & control*; D009504:Neutrophils / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012712:Serum Globulins / Q000378:metabolism*; D014771:Virion / Q000187:drug effects / Q000502:physiology
D037222:Collectins; D006023:Glycoproteins; D010446:Peptide Fragments; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011993:Recombinant Fusion Proteins; D012712:Serum Globulins; C024014:conglutinin; D006861:Hydrogen Peroxide