Relevance of host cell surface glycan structure for cell specificity of influenza A virus

Kastner, Markus; Karner, Andreas; Zhu, Rong; Huang, Qiang; Zhang, D; Liu, J; Geissner, Andreas; Sadewasser, Anne; Lesch, Markus; Woermann, X; Karlas, Alexander; Seeberger, Peter H.; Wolff, Thorsten; Hinterdorfer, Peter; Herrmann, Andreas; Sieben, Christian

doi:10.1101/203349

Cited by 4 publications

(7 citation statements)

References 39 publications

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“…Many pathogens, including the malaria parasite Plasmodium falciparum (Beeson et al 2000) and the bacterium H. pylori (Simon et al 1997), initiate infection by binding host cell glycans. Cell surface glycans can also act as specific receptors for viral hemagglutinins, such as in the cases of influenza virus (Kastner et al 2017, Varki 1993 and human immunodeficiency virus (HIV) (Bode et al 2012), as well as microbial cytotoxins, such as cholera toxin (Fishman & Atikkan 1980, Varki 1993. The glycans of secreted glycoconjugates like mucin are postulated to act as decoys for such pathogens, diverting the binding of the pathogen or toxin away from target cell surfaces (Varki 1993(Varki , 2006 or agglutinating pathogens for mucus clearance, thereby protecting the underlying epithelial cells.…”

Section: Mechanisms Of Mucin-microbe Interactionsmentioning

confidence: 99%

Mucins and Their Role in Shaping the Functions of Mucus Barriers

Wagner

Wheeler

Ribbeck

2018

Annu. Rev. Cell Dev. Biol.

197

158

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We review what is currently understood about how the structure of the primary solid component of mucus, the glycoprotein mucin, gives rise to the mechanical and biochemical properties of mucus that are required for it to perform its diverse physiological roles. Macroscale processes such as lubrication require mucus of a certain stiffness and spinnability, which are set by structural features of the mucin network, including the identity and density of cross-links and the degree of glycosylation. At the microscale, these same features affect the mechanical environment experienced by small particles and play a crucial role in establishing an interaction-based filter. Finally, mucin glycans are critical for regulating microbial interactions, serving as receptor binding sites for adhesion, as nutrient sources, and as environmental signals. We conclude by discussing how these structural principles can be used in the design of synthetic mucin-mimetic materials and provide suggestions for directions of future work in this field.

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Section: Mechanisms Of Mucin-microbe Interactionsmentioning

confidence: 99%

Mucins and Their Role in Shaping the Functions of Mucus Barriers

Wagner

Wheeler

Ribbeck

2018

Annu. Rev. Cell Dev. Biol.

197

158

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“…SA is the terminal sugar on highly diverse sugar structures, 9 and the underlying glycans are known to impact influenza virus binding. 85,86 While binding to α-2,6-sialyllactose (SL) was reduced in mutant viruses L1 and L2 compared to WT virus and nearly abolished by L3 (Figure 5, array 1), it was still one of the few glycans that was at least partly shared between wild-type and mutant viruses. Furthermore, we rationalized that SL serves as a structure bound by a variety of viruses on a variety of glycan arrays.…”

Section: ■ Resultsmentioning

confidence: 99%

“…Toward our goal to render PG-based IAV inhibitors less susceptible toward HA amino acid variations and thereby to potentially broaden the number of susceptible strains, we sought to change the functionalization of and the presentation by the PGs. SA is the terminal sugar on highly diverse sugar structures, and the underlying glycans are known to impact influenza virus binding. , While binding to α-2,6-sialyllactose (SL) was reduced in mutant viruses L1 and L2 compared to WT virus and nearly abolished by L3 (Figure , array 1), it was still one of the few glycans that was at least partly shared between wild-type and mutant viruses. Furthermore, we rationalized that SL serves as a structure bound by a variety of viruses on a variety of glycan arrays .…”

Section: Resultsmentioning

confidence: 99%

“…The low-density array was printed at the Max Planck Institute of Colloids and Interfaces and analyzed as described previously. 85 Of each virus, 2 × 10 6 PFU were loaded on the lowdensity array, which amounted to the same HA titer. Fluorescence images were obtained using a GenePix microarray scanner (Molecular Devices) and analyzed with the GenePix pro 7.2 software.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Evaluation of Multivalent Sialylated Polyglycerols for Resistance Induction in and Broad Antiviral Activity against Influenza A Viruses

et al. 2021

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The development of multivalent sialic acid-based inhibitors active against a variety of influenza A virus (IAV) strains has been hampered by high genetic and structural variability of the targeted viral hemagglutinin (HA). Here, we addressed this challenge by employing sialylated polyglycerols (PGs). Efficacy of prototypic PGs was restricted to a narrow spectrum of IAV strains. To understand this restriction, we selected IAV mutants resistant to a prototypic multivalent sialylated PG by serial passaging. Resistance mutations mapped to the receptor binding site of HA, which was accompanied by altered receptor binding profiles of mutant viruses as detected by glycan array analysis. Specifying the inhibitor functionalization to 2,6-α-sialyllactose (SL) and adjusting the linker yielded a rationally designed inhibitor covering an extended spectrum of inhibited IAV strains. These results highlight the importance of integrating virological data with chemical synthesis and structural data for the development of sialylated PGs toward broad anti-influenza compounds.

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“…Basing on known AFM measurements, for the spherical virus capsid deformation, force-displacement behavior during loading is close to linear (Schaap et al [8]). Close to linear capsid deformation behavior during unloading was observed for /X174, MS2, and Aichi virus (Attinti et al [11]), Influenza A virus (Kastner et al [12]). The paper presents descriptions of elastic deformation of spikes and capsid.…”

Section: Loading Capsid Deformationmentioning

confidence: 96%

Numerical modeling of coronavirus interaction mechanics with a host human cell

Jasevičius

2020

Mechanics of Advanced Materials and Structures

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A numerical study of the interaction of the virus with the cell is presented. The cell was selected for human circulatory endothelium, while the virus was selected close to SARS-CoV-2. The environment in which the virus interacts is close to the blood. A numerical experiment of the interaction was carried out using the DEM. The result is an interaction process showing a change in force, displacement, velocity over time. Under various initial conditions, the analysis examines the influence of spikes and drag forces for the interaction of the virus with the cell.

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Relevance of host cell surface glycan structure for cell specificity of influenza A virus

Cited by 4 publications

References 39 publications

Mucins and Their Role in Shaping the Functions of Mucus Barriers

Mucins and Their Role in Shaping the Functions of Mucus Barriers

Evaluation of Multivalent Sialylated Polyglycerols for Resistance Induction in and Broad Antiviral Activity against Influenza A Viruses

Numerical modeling of coronavirus interaction mechanics with a host human cell

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