Soluble Host Defense Lectins in Innate Immunity to Influenza Virus

Ng, Wendy; Tate, Michelle D.; Brööks, Andrëw G.; Reading, Patrick C.

doi:10.1155/2012/732191

Cited by 34 publications

(39 citation statements)

References 143 publications

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“…The hemagglutinin of influenza A viruses bears high-mannose-type N-glycans that are susceptible to host lectins (Ng et al, 2012). In studies employing a retroviral core pseudotyped with the hemagglutinins of the 1918 H1N1 and the H5N1 avian pandemic influenza viruses, WT and H84T BanLec were both very active and equally inhibitory (Figure 2K, L).…”

Section: Resultsmentioning

confidence: 99%

Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity

Swanson

Boudreaux

Salmon

et al. 2015

Cell

138

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Summary A key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions. On the other hand, monovalent interactions and antiviral activity are preserved by retaining other wild-type conformational features and possibly through unique contacts involving the T84 side chain. Through such fine-tuning, target selection and downstream effects of a lectin can be modulated so as to knock down one activity while preserving another, thus providing tools for therapeutics and for understanding the Sugar Code.

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Section: Resultsmentioning

confidence: 99%

Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity

Swanson

Boudreaux

Salmon

et al. 2015

Cell

138

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“…Collectins express carbohydrate recognition domains (CRDs) that bind to mannose-rich glycans on the viral HA and, in some cases, to the neuraminidase (NA) [5], [6], to mediate a range of anti-IAV activities including inhibition of IAV hemagglutination and NA enzyme function, neutralization of virus infectivity, virus aggregation, increased IAV uptake by neutrophils and opsonization of virus to enhance neutrophil respiratory burst responses to IAV [7], [8], [9]. Surfactant protein (SP)-D, a collectin constitutively expressed in the lung, acts as a classical β-type inhibitor against highly glycosylated IAV [10], [11] and contributes to anti-IAV activity in human bronchoalveolar lavage (BAL) fluids [10], [12].…”

Section: Introductionmentioning

confidence: 99%

Serum Amyloid P Is a Sialylated Glycoprotein Inhibitor of Influenza A Viruses

et al. 2013

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Members of the pentraxin family, including PTX3 and serum amyloid P component (SAP), have been reported to play a role in innate host defence against a range of microbial pathogens, yet little is known regarding their antiviral activities. In this study, we demonstrate that human SAP binds to human influenza A virus (IAV) strains and mediates a range of antiviral activities, including inhibition of IAV-induced hemagglutination (HA), neutralization of virus infectivity and inhibition of the enzymatic activity of the viral neuraminidase (NA). Characterization of the anti-IAV activity of SAP after periodate or bacterial sialidase treatment demonstrated that α(2,6)-linked sialic acid residues on the glycosidic moiety of SAP are critical for recognition by the HA of susceptible IAV strains. Other proteins of the innate immune system, namely human surfactant protein A and porcine surfactant protein D, have been reported to express sialylated glycans which facilitate inhibition of particular IAV strains, yet the specific viral determinants for recognition of these inhibitors have not been defined. Herein, we have selected virus mutants in the presence of human SAP and identified specific residues in the receptor-binding pocket of the viral HA which are critical for recognition and therefore susceptibility to the antiviral activities of SAP. Given the widespread expression of α(2,6)-linked sialic acid in the human respiratory tract, we propose that SAP may act as an effective receptor mimic to limit IAV infection of airway epithelial cells.

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“…that can promote uptake of antigens, such as dendritic cells (45)(46)(47)(48)(49). It is known that HA from viruses that are adapted to circulate in humans contains more glycosylation sites in the globular head domain compared to avian HA (44).…”

Section: Discussionmentioning

confidence: 99%

Avian and Human Seasonal Influenza Hemagglutinin Proteins Elicit CD4 T Cell Responses That Are Comparable in Epitope Abundance and Diversity

DiPiazza

Richards

Poulton

et al. 2017

Clin Vaccine Immunol

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Avian influenza viruses remain a significant concern due to their pandemic potential. Vaccine trials have suggested that humans respond poorly to avian influenza vaccines relative to seasonal vaccines. It is important to understand, first, if there is a general deficiency in the ability of avian hemagglutinin (HA) proteins to generate immune responses and, if so, what underlies this defect. This question is of particular interest because it has been suggested that in humans, the poor immunogenicity of H7 vaccines may be due to a paucity of CD4 T cell epitopes. Because of the generally high levels of cross-reactive CD4 T cells in humans, it is not possible to compare the inherent immunogenicities of avian and seasonal HA proteins in an unbiased manner. Here, we empirically examine the epitope diversity and abundance of CD4 T cells elicited by seasonal and avian HA proteins. HLA-DR1 and HLA-DR4 transgenic mice were vaccinated with purified HA proteins, and CD4 T cells to specific epitopes were identified and quantified. These studies revealed that the diversity and abundance of CD4 T cells specific for HA do not segregate on the basis of whether the HA was derived from human seasonal or avian influenza viruses. Therefore, we conclude that failure in responses to avian vaccines in humans is likely due to a lack of cross-reactive CD4 T cell memory perhaps coupled with competition with or suppression of naive, HA-specific CD4 T cells by memory CD4 T cells specific for more highly conserved proteins.

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Soluble Host Defense Lectins in Innate Immunity to Influenza Virus

Cited by 34 publications

References 143 publications

Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity

Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity

Serum Amyloid P Is a Sialylated Glycoprotein Inhibitor of Influenza A Viruses

Avian and Human Seasonal Influenza Hemagglutinin Proteins Elicit CD4 T Cell Responses That Are Comparable in Epitope Abundance and Diversity

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