Multimerization of surfactant protein D, but not its collagen domain, is required for antiviral and opsonic activities related to influenza virus.
Surfactant protein D (SP-D) plays important roles in the initial innate defense against influenza A virus (IAV). The collagen domain of SP-D is probably critical for its homeostatic functions in vivo and has been implicated in the modulation of macrophage responses to SP-D-ligand complexes. For the current studies, we used a panel of rat SP-D mutants lacking all or part of the collagen domain to more specifically evaluate the contributions of this domain to viral interactions. SP-D multimers lacking the collagenous sequence efficiently neutralized Phil82 IAV, promoted neutrophil uptake of IAV, and also potentiated the IAV-induced neutrophil respiratory burst response. A dodecameric mutant with shortened collagenous arms showed enhanced viral aggregation and neuraminidase inhibition, and an increased capacity to inhibit a partially collectin-resistant strain of IAV. By contrast, truncated molecules lacking an N-terminal and collagen domain showed no detectable antiviral and opsonizing activity, despite preservation of lectin activity and detectable viral binding. Thus, multimerization, which is mediated by the N-peptide, is more important than the collagen domain for efficient viral neutralization and opsonization. However, the structure of the collagen domain significantly influences the anti-viral activity of multimerized forms of SP-D.
White
Mitchell
M
Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Kingma
Paul
P
Tecle
Tesfaldet
T
Kacak
Nilgun
N
Linders
Bruce
B
Heuser
John
J
Crouch
Erika
E
Hartshorn
Kevan
K
D000818:Animals; D002460:Cell Line; D004285:Dogs; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology*; D008024:Ligands; D008264:Macrophages / Q000276:immunology; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology*; D009154:Mutation / Q000276:immunology; D009439:Neuraminidase / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000276:immunology*; D051381:Rats; D016897:Respiratory Burst / Q000235:genetics / Q000276:immunology; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000276:immunology
D008024:Ligands; D046912:Multiprotein Complexes; D037663:Pulmonary Surfactant-Associated Protein D; D014764:Viral Proteins; D009439:Neuraminidase