Effects of Sialic Acid Modifications on Virus Binding and Infection

Wasik, Brian R.; Barnard, Karen N.; Parrish, Colin R.

doi:10.1016/j.tim.2016.07.005

Cited by 111 publications

(116 citation statements)

References 96 publications

(101 reference statements)

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“…Free sialic acid is a nutrient source for the antibiotic-associated enteric pathogens Clostridium difficile and Salmonella typhimurium , and can determine pathogen burden in mouse models (McDonald et al, 2016; Ng et al, 2013). Mucosal glycoproteins carrying sialic acid also serve as viral receptors (Wasik et al, 2016). Despite this broad importance, how commensal sialidase activity determines sialic acid levels in the gut lumen is unexplored.…”

Section: Resultsmentioning

confidence: 99%

Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut

Lim

Zimmermann

Barry

et al. 2017

Cell

157

168

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Summary The gut microbiota is implicated in numerous aspects of health and disease, but dissecting these connections is challenging because genetic tools for gut anaerobes are limited. Inducible promoters are particularly valuable tools, because these platforms allow real-time analysis of the contribution of microbiome gene products to community assembly, host physiology, and disease. We developed a panel of tunable expression platforms for the prominent genus Bacteroides in which gene expression is controlled by a synthetic inducer. In the absence of inducer, promoter activity is fully repressed; addition of inducer rapidly increases gene expression by 4 to 5 orders of magnitude. Because the inducer is absent in mice and their diets, Bacteroides gene expression inside the gut can be modulated by providing the inducer in drinking water. We use this system to measure the dynamic relationship between commensal sialidase activity and liberation of mucosal sialic acid, a receptor and nutrient for pathogens.

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Section: Resultsmentioning

confidence: 99%

Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut

Lim

Zimmermann

Barry

et al. 2017

Cell

157

168

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“…Sialic acids are a family of N ‐ or O ‐substituted derivatives of neuraminic acid, which share the common 9‐carbon core structure with a carboxylic acid residue at the C1 position . The substituents are most commonly presented on C4, 5, 7, 8, and 9 positions .…”

Section: Introductionmentioning

confidence: 99%

“…The substituents are most commonly presented on C4, 5, 7, 8, and 9 positions . Modifications at the C5 position determine the primary sialic acid forms, including N ‐acetylneuraminic acid (Neu5Ac), N ‐glycolylneuraminic acid (Neu5Gc), and 2‐keto‐3‐deoxynononic acid (KDN) . Other modifications mainly include the additions of acetyl, sulfate, lactoyl, and methyl groups .…”

Section: Introductionmentioning

confidence: 99%

“…Modifications at the C5 position determine the primary sialic acid forms, including N ‐acetylneuraminic acid (Neu5Ac), N ‐glycolylneuraminic acid (Neu5Gc), and 2‐keto‐3‐deoxynononic acid (KDN) . Other modifications mainly include the additions of acetyl, sulfate, lactoyl, and methyl groups . Variations in substitutions and linkages generate a highly diverse family of sialic acids and over 50 species have been identified in nature .…”

Section: Introductionmentioning

confidence: 99%

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Mass spectrometry for protein sialoglycosylation

Zhang

Wang

et al. 2017

Mass Spectrometry Reviews

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Sialic acids are a family of structurally unique and negatively charged nine-carbon sugars, normally found at the terminal positions of glycan chains on glycoproteins and glycolipids. The glycosylation of proteins is a universal post-translational modification in eukaryotic species and regulates essential biological functions, in which the most common sialic acid is N-acetyl-neuraminic acid (2-keto-5-acetamido-3,5-dideoxy-D-glycero-D-galactononulopyranos-1-onic acid) (Neu5NAc). Because of the properties of sialic acids under general mass spectrometry (MS) conditions, such as instability, ionization discrimination, and mixed adducts, the use of MS in the analysis of protein sialoglycosylation is still challenging. The present review is focused on the application of MS related methodologies to the study of both N- and O-linked sialoglycans. We reviewed MS-based strategies for characterizing sialylation by analyzing intact glycoproteins, proteolytic digested glycopeptides, and released glycans. The review concludes with future perspectives in the field.

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“…In addition to direct interaction with sialic acids on the target cell, respiratory viruses must navigate a respiratory tract that is known to be densely-packed with secreted sialic acid-bearing mucins and free sialylated oligosaccharides (Zanin et al 2016) that could act as decoys for viral HN (Wasik et al 2016). The ability to evade such decoys would depend, in part, on the neuraminidase (sialic acid cleavage) activity of the HN, by allowing the virus to penetrate the mucus barrier and reach the susceptible respiratory epithelial cells.…”

Section: Virus-host Molecular Interactions Affecting Paramyxovirusmentioning

confidence: 99%

Zoonotic Potential of Emerging Paramyxoviruses

Thibault

Watkinson

Moreira-Soto

et al. 2017

Advances in Virus Research

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The risk of spillover of enzootic paramyxoviruses, and the susceptibility of recipient human and domestic animal populations, are defined by a broad collection of ecological and molecular factors that interact in ways that are not yet fully understood. Nipah and Hendra viruses were the first highly-lethal zoonotic paramyxoviruses discovered in modern times, but other paramyxoviruses from multiple genera are present in bats and other reservoirs that have unknown potential to spill over into humans. We outline our current understanding of paramyxovirus reservoir hosts and the ecological factors that may drive spillover, and we explore the molecular barriers to spillover that emergent paramyxoviruses may encounter. By outlining what is known about enzootic paramyxovirus receptor usage, mechanisms of innate immune evasion, and other host-specific interactions, we highlight the breadth of unexplored avenues that may be important in understanding paramyxovirus emergence.

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Effects of Sialic Acid Modifications on Virus Binding and Infection

Cited by 111 publications

References 96 publications

Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut

Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut

Mass spectrometry for protein sialoglycosylation

Zoonotic Potential of Emerging Paramyxoviruses

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