scholarly journals Conformational Changes of Murine Polyomavirus Capsid Proteins Induced by Sialic Acid Binding

2004 ◽  
Vol 279 (40) ◽  
pp. 41573-41579 ◽  
Author(s):  
Michaela Cavaldesi ◽  
Maddalena Caruso ◽  
Olga Sthandier ◽  
Paolo Amati ◽  
Marie Isabelle Garcia
Keyword(s):  
Sialic Acid ◽  
Conformational Changes ◽  
Capsid Proteins ◽  
Sialic Acid Binding ◽  
Murine Polyomavirus

scholarly journals A Monoclonal Antibody Specific for Reovirus Outer-Capsid Protein ς3 Inhibits ς1-Mediated Hemagglutination by Steric Hindrance

2001 ◽  
Vol 75 (14) ◽  
pp. 6625-6634 ◽  
Author(s):  
Emma L. Nason ◽  
J. Denise Wetzel ◽  
S. K. Mukherjee ◽  
Erik S. Barton ◽  
B. V. Venkataram Prasad ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Sialic Acid ◽  
Capsid Protein ◽  
Conformational Changes ◽  
Steric Hindrance ◽  
Host Cells ◽  
Capsid Proteins ◽  
Outer Capsid Protein ◽  
Viral Attachment ◽  
Outer Capsid

ABSTRACT Reovirus virions are nonenveloped icosahedral particles consisting of two concentric protein shells, termed outer capsid and core. Outer-capsid protein ς1 is the viral attachment protein and binds carbohydrate molecules on the surface of host cells. Monoclonal antibody (MAb) 4F2, which is specific for outer-capsid protein ς3, blocks the binding of ς1 protein to sialic acid and inhibits reovirus-induced hemagglutination (HA). To determine whether MAb 4F2 inhibits HA by altering ς1-ς3 interactions or by steric hindrance, we analyzed the effect of 4F2 immunoglobulin G (IgG) and Fab fragments (Fabs) on HA induced by reovirus strain type 3 Dearing (T3D). The concentration of 4F2 IgG sufficient to inhibit T3D-induced HA was 12.5 μg per ml, whereas that of Fabs was >200 μg per ml. Dynamic light scattering analysis showed that at the concentration of IgG sufficient to inhibit HA, virion-antibody complexes were monodispersed and not aggregated. The affinity of 4F2 Fabs for T3D virions was only threefold less than that of intact IgG, which suggests that differences in HA inhibition titer exhibited by 4F2 IgG and Fabs are not attributable to differences in the affinity of these molecules for T3D virions. We used cryoelectron microscopy and three-dimensional image analysis to visualize T3D virions alone and in complex with either IgG or Fabs of MAb 4F2. IgG and Fabs bind the same site at the distal portion of ς3, and binding of IgG and Fabs induces identical conformational changes in outer-capsid proteins ς3 and μ1. These results suggest that MAb 4F2 inhibits reovirus binding to sialic acid by steric hindrance and provide insight into the conformational flexibility of reovirus outer-capsid proteins.

scholarly journals Structure Analysis of the Major Capsid Proteins of Human Polyomaviruses 6 and 7 Reveals an Obstructed Sialic Acid Binding Site

2014 ◽  
Vol 88 (18) ◽  
pp. 10831-10839 ◽  
Author(s):  
L. J. Stroh ◽  
U. Neu ◽  
B. S. Blaum ◽  
M. H. C. Buch ◽  
R. L. Garcea ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Binding Site ◽  
Structure Analysis ◽  
Capsid Proteins ◽  
Sialic Acid Binding ◽  
Human Polyomaviruses

scholarly journals Probing the Sialic Acid Binding Site of the Hemagglutinin-Neuraminidase of Newcastle Disease Virus: Identification of Key Amino Acids Involved in Cell Binding, Catalysis, and Fusion

2002 ◽  
Vol 76 (4) ◽  
pp. 1816-1824 ◽  
Author(s):  
Helen Connaris ◽  
Toru Takimoto ◽  
Rupert Russell ◽  
Susan Crennell ◽  
Ibrahim Moustafa ◽  
...  
Keyword(s):  
Amino Acids ◽  
Sialic Acid ◽  
Newcastle Disease Virus ◽  
Binding Site ◽  
Disease Virus ◽  
Receptor Binding ◽  
Conformational Changes ◽  
Newcastle Disease ◽  
Coat Proteins ◽  
Sialic Acid Binding

ABSTRACT We recently reported the first crystal structure of a paramyxovirus hemagglutinin-neuraminidase (HN) from Newcastle disease virus. This multifunctional protein is responsible for binding to cellular sialyl-glycoconjugate receptors, promotion of fusion through interaction with the second viral surface fusion (F) glycoprotein, and processing progeny virions by removal of sialic acid from newly synthesized viral coat proteins. Our structural studies suggest that HN possesses a single sialic acid recognition site that can be switched between being a binding site and a catalytic site. Here we examine the effect of mutation of several conserved amino acids around the binding site on the hemagglutination, neuraminidase, and fusion functions of HN. Most mutations around the binding site result in loss of neuraminidase activity, whereas the effect on receptor binding is more variable. Residues E401, R416, and Y526 appear to be key for receptor binding. The increase in fusion promotion seen in some mutants that lack receptor binding activity presents a conundrum. We propose that in these cases HN may be switched into a fusion-promoting state through a series of conformational changes that propagate from the sialic acid binding site through to the HN dimer interface. These results further support the single-site model and suggest certain residues to be important for the triggering of fusion.

scholarly journals POS0744 A NEGATIVE INTERFERON BIOMARKER CD169 / SIGLEC-1 RULES OUT SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 623.2-624
Author(s):  
L. Zorn-Pauly ◽  
A. S. L. Von Stuckrad ◽  
J. Klotsche ◽  
T. Rose ◽  
T. Kallinich ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Sialic Acid ◽  
Lupus Erythematosus ◽  
Predictive Value ◽  
Classification Criteria ◽  
Initial Diagnosis ◽  
Type I ◽  
Systemic Lupus ◽  
Potential Biomarker ◽  
Sialic Acid Binding

Background:While there have been advances in the therapy of systemic lupus erythematosus (SLE) in recent years, there have been no major new findings in SLE biomarkers [1, 2]. Type I interferon (IFN) plays a pivotal role in the pathogenesis of SLE [3]. In 2008, we first described CD169 / SIGLEC-1 (sialic acid-binding immunoglobulin-like lectin-1), an interferon-induced adhesion molecule on monocytes in SLE patients [4]. For over five years SIGLEC-1 has been routinely assessed in our clinic.Objectives:To evaluate and compare the diagnostic utility of the type I IFN induced SIGLEC-1 with established biomarkers in the initial diagnosis of the disease.Methods:We analyzed retrospectively 232 patients who were on suspicion of SLE at Charité University Hospital Berlin between October 2015 and September 2020. Patients underwent full clinical characterization, and biomarkers were determined in the routine laboratory. Based on the final diagnosis, we divided patients into two groups: A) initial diagnosis of SLE and B) Non-SLE mimicking condition.Results:In 76 patients (32.3 %) SLE was confirmed by fulfilling the EULAR / ACR 2019 classification criteria [5]. SIGLEC-1 was dramatically increased in patients with an initial diagnosis of SLE compared to patients without SLE (p<0.0001). For a threshold of 2500 molecule per monocyte, a sensitivity of 98.7 %, a specificity of 82.1 %, a negative predictive value (NPV) of 99.2 %, and a positive predictive value (PPV) of 72.8 % were calculated for SIGLEC-1. Adjusted to the prevalence of SLE in Germany (36.7 per 100,000 inhabitants [6]) NPV and PPV turned out to > 99.9 % and 0.2 %. We further aimed to compare not only the performance of the tests at a given cutoff but also across all possible measured values. Therefore, we conducted ROC curves analyses (see figure 1). The area under the curve (AUC) of SIGLEC-1 test was significantly higher than that of ANA test (AUC=0.88, p=0.031), C3 (AUC = 0.83, p=0.001), C4 (AUC=0.83, p=0.002), but not than that of the Anti-dsDNA ELISA (AUC=0.90, p=0.163).Conclusion:Our study shows that IFN activity is a hallmark at the onset of the disease and that the interferon biomarker SIGLEC-1 is valuable to rule out SLE in suspected cases.References:[1]Ostendorf L, Burns M, Durek P, Heinz GA, Heinrich F, Garantziotis P, Enghard P, Richter U, Biesen R, Schneider U et al: Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus. N Engl J Med 2020, 383(12):1149-1155.[2]Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok CC, Santiago MB et al: Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med 2020, 383(12):1117-1128.[3]Ronnblom L, Leonard D: Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci Med 2019, 6(1):e000270.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, Haupl T, Rudwaleit M, Riemekasten G, Radbruch A et al: Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum 2008, 58(4):1136-1145.[5]Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL et al: 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Annals of the Rheumatic Diseases 2019, 78(9):1151-1159.[6]Brinks R, Fischer-Betz R, Sander O, Richter JG, Chehab G, Schneider M: Age-specific prevalence of diagnosed systemic lupus erythematosus in Germany 2002 and projection to 2030. Lupus 2014, 23(13):1407-1411.Disclosure of Interests:None declared

scholarly journals Neutrophils do not bind to or phagocytize human immune complexes formed with influenza virus

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1639-1646 ◽  
Author(s):  
DR Ratcliffe ◽  
J Michl ◽  
EB Cramer
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Epithelial Cells ◽  
Binding Site ◽  
Immune Complexes ◽  
Human Neutrophils ◽  
Sialic Acid Binding ◽  
Infected Cells ◽  
Neutrophil Adherence ◽  
Human Immune

Abstract Neutrophils appear to form the first line of defense against influenza virus, yet it is unclear how these leukocytes recognize influenza- infected cells. While demonstrating that neutrophils adhere specifically to the sialic acid-binding site on the hemagglutinin molecule (HA) on the surface of influenza-infected (WSN[H1N1]) epithelial cells and not to other viral or epithelial cell antigens, it was observed that human neutrophils do not recognize immune complexes formed with influenza virus. Intact antibodies (mouse monoclonal antibodies [MoAbs] IgG1 and IgG2b, human immune heat-inactivated serum [predominantly IgG1], and IgG purified from human immune serum) that block the sialic acid-binding site on HA significantly reduced (> 80%) neutrophil adherence to influenza-infected epithelial cells. Binding and phagocytosis of free influenza virions and neutrophil agglutination by influenza virus were completely prevented by these antibodies. Intact and F(ab')2 fragments of mouse MoAbs to other viral epitopes caused increased neutrophil adherence to infected cells. This binding was eliminated by F(ab'2) fragments of MoAbs against the sialic acid- binding site on HA, but not by saturating amounts of MoAbs, which block the neutrophil Fc receptors. Thus, it appears that human neutrophils show little ability to bind via their Fc receptors to the immune complexes formed with antibody and either influenza-infected epithelial cells or the free virion. These findings are in contrast to the general dogma, and are the first example of antibody opsonization reducing, rather than enhancing, neutrophil binding and phagocytosis of a pathogen.

scholarly journals Mutations That Affect the Tropism of DA and GDVII Strains of Theiler's Virus In Vitro Influence Sialic Acid Binding and Pathogenicity

2002 ◽  
Vol 76 (16) ◽  
pp. 8138-8147 ◽  
Author(s):  
Karima Jnaoui ◽  
Muriel Minet ◽  
Thomas Michiels
Keyword(s):  
Sialic Acid ◽  
Demyelinating Disease ◽  
Binding Capacity ◽  
Single Amino Acid ◽  
Sialic Acid Binding ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System ◽  
Different Strains ◽  
Single Amino Acid Mutation

ABSTRACT Theiler's murine encephalomyelitis virus (TMEV) is a natural pathogen of the mouse. The different strains of TMEV are divided into two subgroups according to the pathology they provoke. The neurovirulent strains GDVII and FA induce an acute fatal encephalitis, while persistent strains, like DA and BeAn, cause a chronic demyelinating disease associated with viral persistence in the central nervous system. Different receptor usage was proposed to account for most of the phenotype difference between neurovirulent and persistent strains. Persistent but not neurovirulent strains were shown to bind sialic acid. We characterized DA and GDVII derivatives adapted to grow on CHO-K1 cells. Expression of glycosaminoglycans did not influence infection of CHO-K1 cells by parental and adapted viruses. Mutations resulting from adaptation of DA and GDVII to CHO-K1 cells notably mapped to the well-characterized VP1 CD and VP2 EF loops of the capsid. Adaptation of the DA virus to CHO-K1 cells correlated with decreased sialic acid usage for entry. In contrast, adaptation of the GDVII virus to CHO-K1 cells correlated with the appearance of a weak sialic acid usage for entry. The sialic acid binding capacity of the GDVII variant resulted from a single amino acid mutation (VP1-51, Asn→Ser) located out of the sialic acid binding region defined for virus DA. Mutations affecting tropism in vitro and sialic acid binding dramatically affected the persistence and neurovirulence of the viruses.

scholarly journals SIAE Rare Variants in Juvenile Idiopathic Arthritis and Primary Antibody Deficiencies

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Eirini Sevdali ◽  
Elena Tsitsami ◽  
Maria Tsinti ◽  
Evangelia Farmaki ◽  
Efimia Papadopoulou-Alataki ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Sialic Acid ◽  
Cell Activation ◽  
Rare Variants ◽  
Primary Antibody ◽  
Healthy Children ◽  
B Cell Activation ◽  
Loss Of Function ◽  
Primary Antibody Deficiencies ◽  
Sialic Acid Binding

Sialic acid acetylesterase (SIAE) deficiency was suggested to lower the levels of ligands for sialic acid-binding immunoglobulin-like receptors, decreasing the threshold for B-cell activation. In humans, studies of rare heterozygous loss-of-function mutations in SIAE gene in common autoimmune diseases, including juvenile idiopathic arthritis (JIA), yielded inconsistent results. Considering the distinct pathogenesis of the two main subtypes of JIA, autoinflammatory systemic (sJIA) and autoimmune oligo/polyarticular (aJIA), and a predisposition to autoimmunity displayed by patients and families with primary antibody deficiencies (PADs), the aim of our study was to analyze whether SIAE rare variants are associated with both the phenotype of JIA and the autoimmunity risk in families with PADs. A cohort of 69 patients with JIA, 117 healthy children, 54 patients, and family members with PADs were enrolled in the study. Three novel SIAE variants (p.Q343P, p.Y495X, and c.1320+33T>C) were found only in patients with aJIA but interestingly also in their healthy relatives without autoimmunity, while none of PAD patients or their relatives carried SIAE defects. Our results show that SIAE rare variants are not causative of autoimmunity as single defects.

scholarly journals Porcine Arterivirus Infection of Alveolar Macrophages Is Mediated by Sialic Acid on the Virus

2004 ◽  
Vol 78 (15) ◽  
pp. 8094-8101 ◽  
Author(s):  
Peter L. Delputte ◽  
Hans J. Nauwynck
Keyword(s):  
Sialic Acid ◽  
Alveolar Macrophages ◽  
Sialic Acids ◽  
Respiratory Syndrome Virus ◽  
Specific Monoclonal Antibody ◽  
Neuraminidase Treatment ◽  
Acid Binding Protein ◽  
Sialic Acid Binding ◽  
High Mannose ◽  
Binding Lectin

ABSTRACT Recently, we showed that porcine sialoadhesin (pSn) mediates internalization of the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) in alveolar macrophages (Vanderheijden et al., J. Virol. 77:8207-8215, 2003). In rodents and humans, sialoadhesin, or Siglec-1, has been described as a macrophage-restricted molecule and to specifically bind sialic acid moieties. In the current study, we investigated whether pSn is a sialic acid binding protein and, whether so, whether this property is important for its function as a PRRSV receptor. Using untreated and neuraminidase-treated sheep erythrocytes, we showed that pSn binds sialic acid. Furthermore, pSn-specific monoclonal antibody 41D3, which blocks PRRSV infection, inhibited this interaction. PRRSV attachment to and infection of porcine alveolar macrophages (PAM) were both shown to be dependent on the presence of sialic acid on the virus: neuraminidase treatment of virus but not of PAM blocked infection and reduced attachment. Enzymatic removal of all N-linked glycans on the virus with N-glycosidase F reduced PRRSV infection, while exclusive removal of nonsialylated N-linked glycans of the high-mannose type with endoglycosidase H had no significant effect. Free sialyllactose and sialic acid containing (neo)glycoproteins reduced infection, while lactose and (neo)glycoproteins devoid of sialic acids had no significant effect. Studies with linkage-specific neuraminidases and lectins indicated that α2-3- and α2-6-linked sialic acids on the virion are important for PRRSV infection of PAM. From these results, we conclude that pSn is a sialic acid binding lectin and that interactions between sialic acid on the PRRS virion and pSn are essential for PRRSV infection of PAM.

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