Interactions of α-, β-, and θ-Defensins with Influenza A Virus and Surfactant Protein D
- 15 June 2009
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 182 (12), 7878-7887
- https://doi.org/10.4049/jimmunol.0804049
Abstract
We have reported that the α-defensins human neutrophil peptides (HNP)-1 and HNP-2 neutralize and aggregate influenza A virus (IAV) and promote uptake of IAV by neutrophils. These α-defensins were also shown to bind to surfactant protein (SP)-D and reduce its antiviral activity. In this study, we examined retrocyclin (RC)1 and RC2, humanized versions of the antiviral θ-defensins found in the leukocytes of certain nonhuman primates. RC1 was just as effective as HNP-1–3 in neutralizing IAV, and RC2 and RC101 (an analog of RC1) were more effective. In contrast, human β-defensins (HBDs) showed less neutralizing activity. Human defensins 5 and 6 (mainly produced by intestinal Paneth cells) had viral neutralizing activity similar to HNP-1–3. Like HNP-1–3, RCs induced viral aggregation and promoted the uptake of IAV by neutrophils. We used surface plasmon resonance to evaluate binding of defensins to SP-D. HBDs, HD6, and HNP-4 bound minimally to SP-D. HNP-1–3 and RCs bound SP-D with high affinity; however, unlike HNP-1 and HNP-2, RCs did not inhibit SP-D antiviral activity. HBDs also did not inhibit antiviral activity of SP-D. Given their strong neutralizing activity and compatibility with SP-D, RCs may provide attractive prototypes for designing therapeutics that can prevent or treat respiratory infections caused by IAV.Keywords
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