Critical role for cross-linking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus

2008 ◽  
Vol 412 (2) ◽  
pp. 323-329 ◽  
Author(s):  
Tesfaldet Tecle ◽  
Mitchell R. White ◽  
Grith Sorensen ◽  
Donald Gantz ◽  
Nilgun Kacak ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Critical Role ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Cross Linking ◽  
Viral Neutralization ◽  
Neutralizing Activity

Collectins are multimeric host defence lectins with trimeric CRDs (carbohydrate-recognition domains) and collagen and N-terminal domains that form higher-order structures composed of four or more trimers. Recombinant trimers composed of only the CRD and adjacent neck domain (termed NCRD) retain binding activity for some ligands and mediate some functional activities. The lung collectin SP-D (surfactant protein D) has strong neutralizing activity for IAVs (influenza A viruses) in vitro and in vivo, however, the NCRD derived from SP-D has weak viral-binding ability and lacks neutralizing activity. Using a panel of mAbs (monoclonal antibodies) directed against the NCRD in the present study we show that mAbs binding near the lectin site inhibit antiviral activity of full-length SP-D, but mAbs which bind other sites on the CRD do not. Two of the non-blocking mAbs significantly increased binding and antiviral activity of NCRDs as assessed by haemagglutination and neuraminidase inhibition and by viral neutralization. mAb-mediated cross-linking also enabled NCRDs to induce viral aggregation and to increase viral uptake by neutrophils and virus-induced respiratory burst responses by these cells. These results show that antiviral activities of SP-D can be reproduced without the N-terminal and collagen domains and that cross-linking of NCRDs is essential for antiviral activity of SP-D with respect to IAV.

scholarly journals Mechanism of binding of surfactant protein D to influenza A viruses: importance of binding to haemagglutinin to antiviral activity

2000 ◽  
Vol 351 (2) ◽  
pp. 449-458 ◽  
Author(s):  
Kevan L. HARTSHORN ◽  
Mitchell R. WHITE ◽  
Dennis R. VOELKER ◽  
John COBURN ◽  
Ken ZANER ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Surfactant Protein ◽  
Systematic Evaluation ◽  
Surfactant Protein D ◽  
Globular Domain ◽  
Influenza A Viruses ◽  
Viral Neutralization ◽  
The Relationship ◽  
Haemagglutination Activity

Collectins are important in the initial containment of a variety of pathogens, including influenza A virus (IAV). We provide the first systematic evaluation of the oligosaccharide-binding sites for pulmonary surfactant protein D (SP-D) on specific IAV coat glycoproteins and define the relationship between this binding and antiviral activity. With the use of several techniques, SP-D was found to bind via its carbohydrate-recognition domain (CRD) to mannosylated, N-linked carbohydrates on the HA1 domain of the haemagglutinin (HA) and on the neuraminidase of IAV. Using a set of IAV strains that differed in the level and site of glycosylation, and a panel of recombinant collectins, we found that binding of SP-D to the globular domain of the HA was critical in mediating the inhibition of viral haemagglutination activity and infectivity. We also demonstrated that the pattern of binding of a collectin to IAV glycoproteins can be modified by altering the monosaccharide-binding affinity of its CRD or by linking the CRD to a different N-terminal/collagen domain. These studies clarify the mechanisms of viral neutralization by collectins and might be useful in engineering collectins for enhanced antiviral activity.

scholarly journals Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

2005 ◽  
Vol 393 (2) ◽  
pp. 545-553 ◽  
Author(s):  
Kevan L. Hartshorn ◽  
Antoon Ligtenberg ◽  
Mitchell R. White ◽  
Martin van Eijk ◽  
Max Hartshorn ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Scavenger Receptor ◽  
Surfactant Protein ◽  
Sialic Acids ◽  
Surfactant Protein D ◽  
Influenza A Viruses ◽  
Viral Neutralization ◽  
Antiviral Activities ◽  
Innate Defence

We previously found that scavenger receptor cysteine-rich gp-340 (glycoprotein-340), isolated from lung or saliva, directly inhibits human IAVs (influenza A viruses). We now show that salivary gp-340 has broad antiviral activity against human, equine and porcine IAV strains. Although lung and salivary gp-340 are identical in protein sequence, salivary gp-340 from one donor had significantly greater antiviral activity against avian-like IAV strains which preferentially bind sialic acids in α(2,3) linkage. A greater density of α(2,3)-linked sialic acids was present on the salivary gp-340 from this donor as compared with salivary gp-340 from another donor or several preparations of lung gp-340. Hence, the specificity of sialic acid linkages on gp-340 is an important determinant of anti-IAV activity. Gp-340 binds to SP-D (surfactant protein D), and we previously showed that lung gp-340 has co-operative interactions with SP-D in viral neutralization and aggregation assays. We now report that salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of SP-D. This effect was associated with greater binding of salivary gp-340 to the carbohydrate recognition domain of SP-D as compared with the binding of lung gp-340. These findings may relate to inter-individual variations in innate defence against highly pathogenic IAV and to effects of aspiration of oral contents on SP-D-mediated lung functions.

scholarly journals Antiviral activity of Ladania067, an extract from wild black currant leaves against influenza A virus in vitro and in vivo

2014 ◽  
Vol 5 ◽  
Author(s):  
Emanuel Haasbach ◽  
Carmen Hartmayer ◽  
Alice Hettler ◽  
Alicja Sarnecka ◽  
Ulrich Wulle ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Black Currant

scholarly journals In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection

2016 ◽  
Vol 185 ◽  
pp. 327-340 ◽  
Author(s):  
Amin Haghani ◽  
Parvaneh Mehrbod ◽  
Nikoo Safi ◽  
Nur Ain Aminuddin ◽  
Azadeh Bahadoran ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Edible Bird’S Nest

scholarly journals The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins

2013 ◽  
Vol 94 (1) ◽  
pp. 40-49 ◽  
Author(s):  
Shweta Tripathi ◽  
Tesfaldet Tecle ◽  
Anamika Verma ◽  
Erika Crouch ◽  
Mitchell White ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Epithelial Cells ◽  
Antiviral Activity ◽  
Influenza A ◽  
Density Lipoprotein ◽  
Surfactant Protein ◽  
Host Defence ◽  
Surfactant Protein D ◽  
Influenza A Viruses ◽  
Cationic Antimicrobial Peptide

LL-37, the only human cathelicidin, is a cationic antimicrobial peptide with antibacterial and antifungal activity. LL-37 is released from neutrophil granules and produced by epithelial cells. It has been implicated in host defence against influenza A virus (IAV) in recent studies. We now demonstrate dose-related neutralizing activity of LL-37 against several seasonal and mouse-adapted IAV strains. The ability of LL-37 to inhibit these IAV strains resulted mainly from direct effects on the virus, since pre-incubation of virus with LL-37 was needed for optimal inhibition. LL-37 bound high-density lipoprotein (HDL), and pre-incubation of LL-37 with human serum or HDL reduced its antiviral activity. LL-37 did not inhibit viral association with epithelial cells as assessed by quantitative RT-PCR or confocal microscopy. This finding contrasted with results obtained with surfactant protein D (SP-D). Unlike collectins or human neutrophil defensins (HNPs), LL-37 did not induce viral aggregation under electron microscopy. In the electron microscopy studies, LL-37 appeared to cause disruption of viral membranes. LL-37 had additive antiviral activity when combined with other innate inhibitors like SP-D, surfactant protein A and HNPs. Unlike HNPs, LL-37 did not bind SP-D significantly. These findings indicate that LL-37 contributes to host defence against IAV through a mechanism distinct from that of SP-D and HNPs.

scholarly journals Surfactant Protein D Increases Phagocytosis of Hypocapsular Cryptococcus neoformans by Murine Macrophages and Enhances Fungal Survival

2009 ◽  
Vol 77 (7) ◽  
pp. 2783-2794 ◽  
Author(s):  
Scarlett Geunes-Boyer ◽  
Timothy N. Oliver ◽  
Guilhem Janbon ◽  
Jennifer K. Lodge ◽  
Joseph Heitman ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Defense Mechanisms ◽  
Protein A ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Phagocytic Cells

ABSTRACT Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonary infection. C. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan, which constitutes approximately 90% of the capsular material. In the lungs, surfactant protein A (SP-A) and SP-D contribute to immune defense by facilitating the aggregation, uptake, and killing of many microorganisms by phagocytic cells. We hypothesized that SP-D plays a role in C. neoformans pathogenesis by binding to and enhancing the phagocytosis of the yeast. Here, the abilities of SP-D to bind to and facilitate the phagocytosis and survival of the wild-type encapsulated strain H99 and the cap59Δ mutant hypocapsular strain are assessed. SP-D binding to cap59Δ mutant cells was approximately sixfold greater than binding to wild-type cells. SP-D enhanced the phagocytosis of cap59Δ cells by approximately fourfold in vitro. To investigate SP-D binding in vivo, SP-D−/− mice were intranasally inoculated with Alexa Fluor 488-labeled cap59Δ or H99 cells. By confocal microscopy, a greater number of phagocytosed C. neoformans cells in wild-type mice than in SP-D−/− mice was observed, consistent with in vitro data. Interestingly, SP-D protected C. neoformans cells against macrophage-mediated defense mechanisms in vitro, as demonstrated by an analysis of fungal viability using a CFU assay. These findings provide evidence that C. neoformans subverts host defense mechanisms involving surfactant, establishing a novel virulence paradigm that may be targeted for therapy.

scholarly journals Antiviral activity of Chongkukjang extracts against influenza A virus in vitro and in vivo

2015 ◽  
Vol 2 (2) ◽  
pp. 47-51 ◽  
Author(s):  
Bai Wei ◽  
Se-Yeoun Cha ◽  
Min Kang ◽  
Young Jin Kim ◽  
Chang-Won Cho ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A

scholarly journals Histone H4 potentiates neutrophil inflammatory responses to influenza A virus: Down-modulation by H4 binding to C-reactive protein and Surfactant protein D

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247605
Author(s):  
I-Ni Hsieh ◽  
Mitchell White ◽  
Marloes Hoeksema ◽  
Xavier Deluna ◽  
Kevan Hartshorn
Keyword(s):  
Influenza A Virus ◽  
Respiratory Burst ◽  
Influenza A ◽  
Inflammatory Responses ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Histone H4 ◽  
C Reactive Protein ◽  
Reactive Protein

Neutrophils participate in the early phase of the innate response to uncomplicated influenza A virus (IAV) infection but also are a major component in later stages of severe IAV or COVID 19 infection where neutrophil extracellular traps (NETs) and associated cell free histones are highly pro-inflammatory. It is likely that IAV interacts with histones during infection. We show that histone H4 binds to IAV and aggregates viral particles. In addition, histone H4 markedly potentiates IAV induced neutrophil respiratory burst responses. Prior studies have shown reactive oxidants to be detrimental during severe IAV infection. C reactive protein (CRP) and surfactant protein D (SP-D) rise during IAV infection. We now show that both of these innate immune proteins bind to histone H4 and significantly down regulate respiratory burst and other responses to histone H4. Isolated constructs composed only of the neck and carbohydrate recognition domain of SP-D also bind to histone H4 and partially limit neutrophil responses to it. These studies indicate that complexes formed of histones and IAV are a potent neutrophil activating stimulus. This finding could account for excess inflammation during IAV or other severe viral infections. The ability of CRP and SP-D to bind to histone H4 may be part of a protective response against excessive inflammation in vivo.

Antiviral activities of pyridine fused and pyridine containing heterocycles, a review (From 2000 to 2020)

2021 ◽  
Vol 21 ◽  
Author(s):  
Seyedeh Roya Alizadeh ◽  
Mohammad Ali Ebrahimzadeh
Keyword(s):  
Antiviral Activity ◽  
Biological Activities ◽  
Critical Role ◽  
Antiviral Agents ◽  
Rnase H ◽  
Pyridine Derivatives ◽  
Action Mechanism ◽  
Syncytial Virus

: Heterocyclic compounds play a critical role in medicinal chemistry and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound pyridine showed various applications that acts as an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals. Due to the increase of drug resistance, there is an obvious medical need to develop new antiviral agents. Various derivatives of pyridine scaffold display abroad biological activities such as anti-microbial, anti-viral, antioxidant, anti-diabetic, anti-cancer, anti-malaria, analgesic and anti-inflammatory activities, psychopharmacological antagonistic, anti-amoebic agents, and anti-thrombic activity. Due to the high importance of pyridine derivatives, in the present review, we tried to collect and classify many pyridine derivatives based on their structures from 2000 to 2020. Pyridine derivatives were classified into two general categories including pyridine containing heterocycles and pyridine fused rings. Structure-activity relationship (SAR) and the action mechanism of derivatives were also investigated. According to the recent studies, these derivatives exhibited good antiviral activity against different types of viruses such as the human immunodeficiency viruses (HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), Respiratory syncytial virus (RSV), and Cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism such as RT inhibition, polymerase inhibition, Inhibition of RNase H activity, inhibition of maturation, inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6, CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally inhibition of viral replication cycle. This paper summarily expressed the past and present results about the discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the evaluations were performed by way of in vitro testing and is necessary to investigate in vivo and clinical testing for having better evaluations in the future. We believe that pyridine derivatives can be used as promising antiviral agents and needs to perform more broad investigations in this field.

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