scholarly journals Mannose-Binding Lectin in Severe Acute Respiratory Syndrome Coronavirus Infection

2005 ◽  
Vol 191 (10) ◽  
pp. 1697-1704 ◽  
Author(s):  
W. K. Eddie Ip ◽  
Kwok Hung Chan ◽  
Helen K. W. Law ◽  
Gloria H. W. Tso ◽  
Eric K. P. Kong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Serum Levels ◽  
Mannose Binding Lectin ◽  
In Vitro Assays ◽  
Calcium Dependent ◽  
Control Subjects ◽  
Mannose Binding ◽  
Carbohydrate Recognition Domains ◽  
Binding Lectin

Abstract Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS

scholarly journals Association between Mannose-Binding Lectin Gene Polymorphisms and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection

2005 ◽  
Vol 192 (8) ◽  
pp. 1355-1361 ◽  
Author(s):  
Hongxing Zhang ◽  
Gangqiao Zhou ◽  
Lianteng Zhi ◽  
Hao Yang ◽  
Yun Zhai ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Gene Polymorphisms ◽  
Direct Sequencing ◽  
Population Attributable Fraction ◽  
Mannose Binding Lectin ◽  
Promoter Polymorphisms ◽  
Homogeneous Population ◽  
Control Subjects ◽  
Mannose Binding ◽  
Binding Lectin

Abstract BackgroundGenetic determinants of susceptibility to severe acute respiratory syndrome coronavirus (SARS-CoV) infection remain unknown. We assessed whether mannose-binding lectin (MBL) gene polymorphisms were associated with susceptibility to SARS-CoV infection or disease severity in an ethnically homogeneous population born in northern China MethodsThe frequencies of 1 mutation in codon 54 and 3 promoter polymorphisms at nt −550, −221, and 4 were ascertained in 352 patients with SARS and 392 control subjects, by means of polymerase chain reaction direct sequencing ResultsOf 352 patients with SARS and 392 control subjects, 120 (34.4%) and 91 (23.2%) were carriers of the codon 54 variant, respectively (odds ratio [OR], 1.73 [95% confidence interval {CI}, 1.25–2.39]; P=.00086). A total of 123 (36.0%) of 352 patients with SARS and 100 (25.5%) of 392 control subjects had haplotype pairs associated with medium or low expression of MBL (OR, 1.67 [95% CI, 1.21–2.29]; P=.00187). The population-attributable fraction of patients with SARS that was associated with having the codon 54 variant was 20.1% (95% CI, 7.9%–32.3%) Conclusions MBL gene polymorphisms were significantly associated with susceptibility to SARS-CoV infection; this might be explained by the reduced expression of functional MBL secondary to having the codon 54 variant

scholarly journals A New Surface Plasmon Resonance Assay for In Vitro Screening of Mannose-Binding Lectin Inhibitors

2016 ◽  
Vol 21 (7) ◽  
pp. 749-757 ◽  
Author(s):  
Matteo Stravalaci ◽  
Daiana De Blasio ◽  
Franca Orsini ◽  
Carlo Perego ◽  
Alessandro Palmioli ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Ischemia Reperfusion ◽  
Mannose Binding Lectin ◽  
Lectin Pathway ◽  
In Vitro Screening ◽  
Mannose Binding ◽  
Binding Lectin

Mannose-binding lectin (MBL) is a circulating protein that acts as a soluble pattern recognition molecule of the innate immunity. It binds to carbohydrate patterns on the surface of pathogens or of altered self-cells, with activation of the lectin pathway of the complement system. Recent evidence indicates that MBL contributes to the pathophysiology of ischemia-reperfusion injury and other conditions. Thus, MBL inhibitors offer promising therapeutic strategies, since they prevent the interaction of MBL with its target sugar arrays. We developed and characterized a novel assay based on surface plasmon resonance for in vitro screening of these compounds, which may be useful before the more expensive and time-consuming in vivo studies. The assay measures the inhibitor’s ability to interfere with the binding of murine MBL-A or MBL-C, or of human recombinant MBL, to mannose residues immobilized on the sensor chip surface. We have applied the assay to measure the IC50 of synthetic glycodendrimers, two of them with neuroprotective properties in animal models of MBL-mediated injuries.

Serum levels of mannose-binding lectin in systemic sclerosis: a possible contribution to the initiation of skin sclerosis in the diffuse cutaneous subtype

2014 ◽  
Vol 24 (1) ◽  
pp. 123-125 ◽  
Author(s):  
Kaname Akamata ◽  
Yoshihide Asano ◽  
Naohiko Aozasa ◽  
Shinji Noda ◽  
Takashi Taniguchi ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Serum Levels ◽  
Mannose Binding Lectin ◽  
Skin Sclerosis ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals Mannose-Binding Lectin Binds to Amyloid Protein and Modulates Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mykol Larvie ◽  
Timothy Shoup ◽  
Wei-Chuan Chang ◽  
Lorencia Chigweshe ◽  
Kevan Hartshorn ◽  
...  
Keyword(s):  
Mannose Receptor ◽  
Tissue Homeostasis ◽  
Mannose Binding Lectin ◽  
Binding Characteristics ◽  
Calcium Dependent ◽  
Rich Domain ◽  
Mannose Binding ◽  
Carbohydrate Ligands ◽  
Binding Lectin ◽  
Cysteine Rich Domain

Mannose-binding lectin (MBL), a soluble factor of the innate immune system, is a pattern recognition molecule with a number of known ligands, including viruses, bacteria, and molecules from abnormal self tissues. In addition to its role in immunity, MBL also functions in the maintenance of tissue homeostasis. We present evidence here that MBL binds to amyloidβpeptides. MBL binding to other known carbohydrate ligands is calcium-dependent and has been attributed to the carbohydrate-recognition domain, a common feature of other C-type lectins. In contrast, we find that the features of MBL binding to Aβare more similar to the reported binding characteristics of the cysteine-rich domain of the unrelated mannose receptor and therefore may involve the MBL cysteine-rich domain. Differences in MBL ligand binding may contribute to modulation of inflammatory response and may correlate with the function of MBL in processes such as coagulation and tissue homeostasis.

Smoking status interacts with the association between mannose-binding lectin serum levels and gene polymorphism and the carriage of oropharyngeal bacteria

2010 ◽  
Vol 71 (3) ◽  
pp. 298-303 ◽  
Author(s):  
Ulla Jounio ◽  
Aino Rantala ◽  
Aini Bloigu ◽  
Raija Juvonen ◽  
Taina Lajunen ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Smoking Status ◽  
Serum Levels ◽  
Mannose Binding Lectin ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals A Single Asparagine-Linked Glycosylation Site of the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Facilitates Inhibition by Mannose-Binding Lectin through Multiple Mechanisms

2010 ◽  
Vol 84 (17) ◽  
pp. 8753-8764 ◽  
Author(s):  
Yanchen Zhou ◽  
Kai Lu ◽  
Susanne Pfefferle ◽  
Stephanie Bertram ◽  
Ilona Glowacka ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Entry ◽  
Cathepsin L ◽  
Glycosylation Site ◽  
Mannose Binding Lectin ◽  
Binding Motif ◽  
Viral Binding ◽  
Mannose Binding ◽  
Viral Envelopes ◽  
Binding Lectin

ABSTRACT Mannose-binding lectin (MBL) is a serum protein that plays an important role in host defenses as an opsonin and through activation of the complement system. The objective of this study was to assess the interactions between MBL and severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein (SARS-S). MBL was found to selectively bind to retroviral particles pseudotyped with SARS-S. Unlike several other viral envelopes to which MBL can bind, both recombinant and plasma-derived human MBL directly inhibited SARS-S-mediated viral infection. Moreover, the interaction between MBL and SARS-S blocked viral binding to the C-type lectin, DC-SIGN. Mutagenesis indicated that a single N-linked glycosylation site, N330, was critical for the specific interactions between MBL and SARS-S. Despite the proximity of N330 to the receptor-binding motif of SARS-S, MBL did not affect interactions with the ACE2 receptor or cathepsin L-mediated activation of SARS-S-driven membrane fusion. Thus, binding of MBL to SARS-S may interfere with other early pre- or postreceptor-binding events necessary for efficient viral entry.

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