Multimerization of surfactant protein D, but not its collagen domain, is required for antiviral and opsonic activities related to influenza virus

Mitchell White, Paul Kingma, Tesfaldet Tecle, Nilgun Kacak, Bruce Linders, John Heuser, Erika Crouch, Kevan Hartshorn

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)7936-7943
Number of pages8
JournalJournal of Immunology
Volume181
Issue number11
StatePublished - Dec 1 2009

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