Role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein D
Surfactant protein D (SP-D) plays an important role in innate defense against influenza A viruses (IAVs) and other pathogens. Genotypic variation between Met and Thr at amino acid 11 in the N-terminus of SP-D is reported to modulate resistance to respiratory infections.
One hypothesis is that this variation affects multimerization of SP-D.
Methods: We compared several various recombinant SP-D preparations for antiviral activities against IAV.
Results: Initially, we prepared Thr11 SP-D trimers and multimers by gel filtration.
Certain activities (e.g ., viral aggregation, neuraminidase (NA) inhibition, and opsonizing activity) were affected much more by multimerization than others (e.g ., hemagglutination inhibition and neutralization). Thr11 and Met11 SP-D were prepared using an alternative method.
These preparations were not fractionated by size and differed subtly in the proportions of various oligomeric forms, but did not differ in antiviral activities. Regardless of source, SP-Ds had strong activity against many recent strains of influenza A and B virus from humans; however, H5N1 strains were resistant.
Of interest, human H3N2 and H1N1 strains obtained shortly after introduction of these subtypes in the human population were resistant to SP-D. H3N2 strains have become steadily more sensitive to SP-D over time in the human population.
In contrast, H1N1 strains became more sensitive after a few years of human circulation whereas more recent strains have become less sensitive. Overall H3N2 and H1N1 strains have gained glycan attachments on their hemagglutinin compared with the initial pandemic strains.
Certain specific sites of glycan attachment appear to correlate with sensitivity to SP-D.
Conclusions: This study defines properties of SP-D important for antiviral activity and indicates sensitivity of novel strains may be predictable from knowledge of their glycosylation.
Further study of the role of specific glycans on the viral HA in mediating sensitivity to host defense lectins will be of great interest since lack of susceptibility could be a contributory factor to virulence of pandemic strains.
Author: Kevan L Hartshorn, Richard Webby, Mitchell R White, Tesfaldet Tecle, Clark Pan, Susan Boucher, Rodney J Moreland, Erika C Crouch and Ronald K Scheule
Credits/Source: Respiratory Research 2008, 9:65
Published on: 2008-09-23
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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