Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses

Nikolaidis, Nikolaos M.; White, Mitchell R.; Allen, Kimberly; Tripathi, Shweta; Qi, Li; McDonald, Barbara; Taubenberger, Jeffery K.; Seaton, Barbara A.; McCormack, Francis X.; Crouch, Erika C.; Hartshorn, Kevan L.

doi:10.1152/ajplung.00035.2014

Cited by 19 publications

(31 citation statements)

References 29 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have found that D325A(orS) þ R343V and R343V can inhibit replication of Cal09 in respiratory epithelial cells, presumably reflecting their greater ability to bind to the single oligosaccharide present on the head region of Cal09. 44 In keeping with this the mutant NCRDs were able to inhibit replication of Cal09 in monocytes, while full-length SP-D could not. 44 H-ficolin was able to increase uptake of PR-8 but not the Phil82 strain of IAV by neutrophils and monocytes.…”

Section: Discussionmentioning

confidence: 60%

See 1 more Smart Citation

Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production

et al. 2016

Self Cite

View full text Add to dashboard Cite

Infiltrating activated monocytes are important mediators of damaging inflammation during influenza A virus (IAV) infection. We show that soluble respiratory proteins [collectins, surfactant proteins D (SP-D) and mannose binding lectin (MBL), H-ficolin and LL-37] inhibit replication of seasonal IAV in human monocytes. The collectins and H-ficolin also increased viral uptake by the cells, while LL-37 did not. H-ficolin was able to inhibit replication of the 2009 pandemic H1N1 strain (Cal09) in monocytes, but SP-D and LL-37 had significantly fewer inhibitory effects on this strain than on seasonal IAV. All of these proteins reduced IAV-induced TNF-α production, even in instances when viral replication was not reduced. We used modified recombinant versions of SP-D, MBL and ficolin to elucidate mechanisms through which these proteins alter monocyte interactions with IAV. We demonstrate the importance of the multimeric structure, and of binding properties of the lectin domain, in mediating antiviral and opsonic activity of the proteins. Hence, soluble inhibitors present in airway lining fluid may aid clearance of IAV by promoting monocyte uptake of the virus, while reducing viral replication and virus-induced TNF-α responses in these cells. However, SP-D and LL-37 have reduced ability to inhibit replication of pandemic IAV in monocytes.

show abstract

Section: Discussionmentioning

confidence: 60%

“…44 In keeping with this the mutant NCRDs were able to inhibit replication of Cal09 in monocytes, while full-length SP-D could not. 44 H-ficolin was able to increase uptake of PR-8 but not the Phil82 strain of IAV by neutrophils and monocytes. This is in keeping with its different mechanism of viral attachment to IAV.…”

Section: Discussionmentioning

confidence: 60%

Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…SP-D is also known to inhibit IAV by binding its surface glycoproteins HA and NA (15, 31, 20, 47). For this study, a recombinant full length human SP-D (rhSPDII) that exists as dodecamers was prepared, as described previously by Nikolaidis et al (48, 49). In addition to the full-length SP-D, recombinant neck and carbohydrate recognition domain (NCRD) from SP-D were also used.…”

Section: Methodsmentioning

confidence: 99%

“…These NCRDs lack the N -terminal domain and the extended collagen domain present in the full-length SP-D and as a result form homotrimers instead of higher order multimers. The wild-type recombinant human NCRD (huNCRD) has been shown to bind glycans but lacks antiviral activity because of absence of cooperative binding effect from the multiple heads (49–51). Gain-of-function mutants R343V and double mutant D325A+R343V (D+R), which have been shown to possess increased virus binding and neutralizing activity (48, 49, 52–54), were also used in bioassays.…”

Section: Methodsmentioning

confidence: 99%

Integrated Omics and Computational Glycobiology Reveal Structural Basis for Influenza A Virus Glycan Microheterogeneity and Host Interactions

Khatri

Klein

White

et al. 2016

Molecular & Cellular Proteomics

Self Cite

114

View full text Add to dashboard Cite

Despite sustained biomedical research effort, influenza A virus remains an imminent threat to the world population and a major healthcare burden. The challenge in developing vaccines against influenza is the ability of the virus to mutate rapidly in response to selective immune pressure. Hemagglutinin is the predominant surface glycoprotein and the primary determinant of antigenicity, virulence and zoonotic potential. Mutations leading to changes in the number of HA glycosylation sites are often reported. Such genetic sequencing studies predict at best the disruption or creation of sequons for N-linked glycosylation; they do not reflect actual phenotypic changes in HA structure. Therefore, combined analysis of glycan micro and macro-heterogeneity and bioassays will better define the relationships among glycosylation, viral bioactivity and evolution. We present a study that integrates proteomics, glycomics and glycoproteomics of HA before and after adaptation to innate immune system pressure. We combined this information with glycan array and immune lectin binding data to correlate the phenotypic changes with biological activity. Underprocessed glycoforms predominated at the glycosylation sites found to be involved in viral evolution in response to selection pressures and interactions with innate immune-lectins. To understand the structural basis for site-specific glycan microheterogeneity at these sites, we performed structural modeling and molecular dynamics simulations. We observed that the presence of immature, high-mannose type glycans at a particular site correlated with reduced accessibility to glycan remodeling enzymes. Further, the high mannose glycans at sites implicated in immune lectin recognition were predicted to be capable of forming trimeric interactions with the immune-lectin surfactant protein-D.

show abstract

“…Antiviral responses are initiated, including the release of antimicrobial peptides such as surfactants, mucins, LL-37 and β-defensins, which decrease viral binding to epithelial cells and promote recruitment of innate immune cells such as neutrophils [47,50,51]. Surfactant proteins are capable of binding to virus, which helps to limit infectivity and disease severity [52][53][54][55]. Upon infection, respiratory epithelial cells sense virus through Toll-Like Receptors (TLRs), retinoic acid-inducible gene I (RIG-I), NOD-like receptors (NLRs), and melanoma differentiation-associated 5 (MDA-5), leading to the expression of type-I and type-III interferons (IFN), interleukin-6 (IL-6), IL-1β, IL-18, and other pro-inflammatory cytokines and chemokines [56][57][58][59].…”

Section: The Host Immune Response To Influenza Virus Infectionmentioning

confidence: 99%

The Importance of Vaccinating Children and Pregnant Women against Influenza Virus Infection

Misra

Nayak

2019

Pathogens

View full text Add to dashboard Cite

Influenza virus infection is responsible for significant morbidity and mortality in the pediatric and pregnant women populations, with deaths frequently caused by severe influenza-associated lower respiratory tract infection and acute respiratory distress syndrome (ARDS). An appropriate immune response requires controlling the viral infection through activation of antiviral defenses, which involves cells of the lung and immune system. High levels of viral infection or high levels of inflammation in the lower airways can contribute to ARDS. Pregnant women and young children, especially those born prematurely, may develop serious complications if infected with influenza virus. Vaccination against influenza will lead to lower infection rates and fewer complications, even if the vaccine is poorly matched to circulating viral strains, with maternal vaccination offering infants protection via antibody transmission through the placenta and breast milk. Despite the health benefits of the influenza vaccine, vaccination rates around the world remain well below targets. Trust in the use of vaccines among the public must be restored in order to increase vaccination rates and decrease the public health burden of influenza.

show abstract

Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses

Cited by 19 publications

References 29 publications

Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production

Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production

Integrated Omics and Computational Glycobiology Reveal Structural Basis for Influenza A Virus Glycan Microheterogeneity and Host Interactions

The Importance of Vaccinating Children and Pregnant Women against Influenza Virus Infection

Contact Info

Product

Resources

About