Viral aggregating and opsonizing activity in collectin trimers

Kevan L. Hartshorn, Mitchell R. White, Tesfaldet Tecle, Grith Sorensen, Uffe Holmskov, Erika C. Crouch

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Collectins are collagenous lectins present in blood, respiratory lining fluid, and other mucosal secretions that play important roles in innate defense against infection. The collectin, surfactant protein D (SP-D), limits infection by viruses and bacteria in the respiratory tract, eye, and female genital tract. Multimeric SP-D has strong antiviral activity and is a potent viral and bacterial agglutinin and opsonin; however, trimers composed of the neck and carbohydrate recognition domain (hSP-D-NCRD) of SP-D lack these activities. We now show that, in contrast, a trimeric neck and CRD construct of bovine serum collectin CL-46 induces aggregation of influenza A virus (IAV) and potently increases IAV uptake by neutrophils. CL-46-NCRD showed calcium-dependent and sugar-sensitive binding to both neutrophils and IAV. Replacement of specific residues of the CRD of human SP-D with those found in bovine serum collectins conferred opsonizing activity. The most effective substitution involved replacement of arginine 343 with valine (hSP-D-NCRD/R343V). hSP-D-NCRD/R343V greatly increased viral uptake by neutrophils and monocytes and also potentiated neutrophil respiratory burst responses. These effects were further increased by cross-linking of hSP-D-NCRD/R343V trimers with MAbs directed against areas of the hSP-D-NCRD not involved in viral binding. Unlike the wild-type human SP-D hSP-D-NCRD, hSP-D-NCRD/R343V also induced viral aggregation. These results indicate that collectins can act as opsonins for IAV even in the absence of the collagen domain or higher order multimerization. This may involve increased affinity of individual CRDs for glycoconjugates displayed on host cells or the viral envelope.

Original languageEnglish
Pages (from-to)L79-L88
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume298
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • CL-46
  • Influenza virus
  • Neutrophils

Fingerprint Dive into the research topics of 'Viral aggregating and opsonizing activity in collectin trimers'. Together they form a unique fingerprint.

  • Cite this