China
Africa
Explore chapters and articles related to this topic
The 1918 Influenza A Pandemic
Published in Patricia G. Melloy, Viruses and Society, 2023
If one examines the structure of an influenza virus, one will see two major kinds of spike proteins coming out of the envelope: the hemagglutinin (H) and neuraminidase (N) proteins. The hemagglutinin spike proteins attach to sialic acid, a type of sugar or carbohydrate, displayed on respiratory cells. The neuraminidase proteins later clear sialic acid molecules out of the way, preventing any obstacles to catch the influenza viral particles as they bud back out of the cell, thousands of viral particles at a time (Barry 2018; Brown 2018; Lostroh 2019). There are sugars bound to proteins and lipids on cell surfaces as well as on secreted molecules. Sialic acid is a type of sugar attached to the “outermost part” of the sugar chain in certain cell types. Sialic acid has a normal role in cell interactions as well as affecting protein stability. However, viral, bacterial, and parasitic pathogens can use sialic acid as a way to gain entry into cells (Varki 2008).
Inherited Differences in Alpha1-Antitrypsin
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
Yoshida et al, [81] and Jeppson [82] have independently determined the amino acid substitution that distinguishes M from Ζ protein. Both used different isolation procedures. Yoshida used Crawford's procedure [14] with minor modifications and Jeppson et al. used the thiol-disulfide interchange procedure [21]. Yoshida et al. reduced and S-carboxymethylated preparations and removed sialic acid by exhaustive treatment with neuraminidase. Trypsin digestion and fingerprinting followed. In five pairs of peptide maps they consistently found a difference in the position of two peptides labeled M-l and M-2 or Z-l and Z-2, respectively. M-l contained glutamic acid instead of lysine in Z-l and M-2 contained glutamic acid instead of glutamine in Z-2.
Progressive multifocal leukoencephalopathy
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Eric M. L. Williamson, Joseph R. Berger
Several steps are hypothesized to occur for a switch from a benign JC virus in the urogenitary system to the neuroinvasive and pathogenic virus associated with PML. The first step of genetic rearrangements of the NCCR in the archetype virus [84,85] seems plausible given that rearrangements to the regulatory region lead to a virus with increased replication capacity in human glia while maintaining low-level expression in kidney. Mutations in the capsid protein VP1 are also seen in patients with PML and likely represent immune escape variants [86–89] that overlap with antibody recognition epitopes and with T cell epitopes important for mounting a cell-mediated response against the virus. Whether these mutant viruses contribute to the development of PML or are the result of high-level JC viral replication associated with PML is unclear. Another possibility is that reduced dependence of the mutants on sialic acid-binding allows them to break out of the kidney and spread more efficiently to the brain.
The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease
Published in International Reviews of Immunology, 2023
Shane Prenzler, Santosh Rudrawar, Mario Waespy, Sørge Kelm, Shailendra Anoopkumar-Dukie, Thomas Haselhorst
The sialic acid binding immunoglobulin-like lectins (Siglec) are a family of transmembrane proteins characterized by an extracellular domain, the transmembrane region and cytoplasmic tail [1]. Sialic acids are a family of nine-carbon acidic monosaccharides that occur naturally at the end of sugar chains attached to the surfaces of cells and soluble proteins and are ligands for Siglec proteins (Figure 1) [2]. Siglec-1, also known as CD169 and Sialoadhesin (Sn), is the first siglec family member identified. Siglec-1 is a 210 kDa type I single membrane spanning glycoprotein containing 17 immunoglobulin-like domains [1, 3]. Expression of Siglec-1 is found primarily on dendritic cells (DCs), macrophages and interferon induced monocytes [4–6]. The structure of Siglec-1 is unique among siglecs and its function as a receptor also is different compared to other receptors in this class, as it contains the most extracellular domains out of all the siglecs [7]. Sixteen of these extracellular domains are C2-set domains and the furthermost domain is the terminal V-set domain which contains the sialic acid binding pocket (Figure 2) [7]. The V-set domain of Siglec-1 is also highly conserved across vertebrate species, similar to Siglec-2 (CD22), Siglec-4 (MAG) and Siglec-15 [8]. Amino acid differences in the human and murine form of Siglec-2 necessitated the development of transgenic CD22 mice which expressed human CD22 [9].
Gut associated metabolites and their roles in Clostridioides difficile pathogenesis
Published in Gut Microbes, 2022
Andrea Martinez Aguirre, Joseph A. Sorg
C. difficile also can use metabolites produced by the host and other gut microbes during colonization.92,95,96 The gut symbiont Bacteroides thetatiotaomicron encodes a sialidase enzyme that cleaves and releases sialic acid from mucosal glycoconjugates. C. difficile encodes a sialic acid catabolic operon. Using a transcriptional analysis of germ free and B. thetatiotaomicron monoassociated mice, the data showed that the ability of B. thetatiotaomicron to release sialic acid resulted in increased expression levels of the C. difficile sialic acid operon.95 Additionally, a spike in free sialic acid 1 day after antibiotic treatment of mice was observed but these levels reduced 3 days after antibiotic treatment.95 Moreover, mice monoassociated with a B. thetatiotaomicron sialidase mutant strain and then infected with C. difficile had lower C. difficile CFU counts (Figure 3(a-d)).95 These results suggest an important role of sialic acid during in vivo infection.
Dietary sialylated oligosaccharides in early-life may promote cognitive flexibility during development in context of obesogenic dietary intake
Published in Nutritional Neuroscience, 2022
Caroline Clouard, Inonge Reimert, Stephen A. Fleming, Sietse-Jan Koopmans, Teun Schuurman, Jonas Hauser
The importance of sialic acid in brain development has been well reviewed. Briefly, 75% of sialic acid is present in the brain in gangliosides, which themselves have critical roles during neurodevelopment for the synthesis and regulation of neurons, synapses, axons, and myelin [48,51]. Though sialic acid can be synthesized de novo, it is believed that exogenous sources may also be required for optimal brain development [51]. In early life, this exogenous source is human milk, in which about ¾ of sialic acid is present in oligosaccharide bound form (i.e. as sialylated milk oligosaccharides), or infant formula, in which sialic acid level is significantly lower [51]. Here, we observed a cognitive promoting effect of early life sialyllactose supplementation specific to a period of sexual development. Adolescence is a known time of great cognitive change and plasticity in the brain [52]. For example, pruning of dendritic spines and loss of synaptic density are well documented in the rodent prefrontal cortex [53,54]. Such changes coincide with improvements in reversal learning during adolescence [45]. Thus, it is tempting to speculate that the effects observed in this study are of a programing effect wherein increased sialyllactose in early life better primed the brain for the synaptic reorganization that occurred during adolescence.