The role of host cell glycans on virus infectivity: The SARS-CoV-2 case

Mapping Intimacies ◽

10.1101/2021.05.08.443212 ◽

2021 ◽

Author(s):

Silvia Acosta Guitierrez ◽

Joseph Buckley ◽

Giuseppe Battaglia

Keyword(s):

Critical Role ◽

Steric Effects ◽

Virus Infectivity ◽

Specific Interactions ◽

Steric Repulsion ◽

Virus Tropism ◽

Repulsive Potentials ◽

Exclusion Effect ◽

Combinatorial Expression

Long and complex chains of sugars, called glycans, often coat both the cell and protein surface. Glycans both modulate specific interactions and protect cells. On the cell surface, these sugars form a cushion known as the glycocalyx. Here, we show that Heparan Sulfate (HS) chains - part of the glycocalyx - and other glycans - expressed on the surface of both host and virus proteins - have a critical role in modulating both attractive and repulsive potentials during viral infection. We analyse the SARS-CoV-2 virus, modelling its spike proteins binding to HS chains and two key entry receptors, ACE2 and TMPRSS2. We include the volume exclusion effect imposed on the HS chains impose during virus insertion into glycocalyx and the steric repulsion caused by changes in the conformation of the ACE2 glycans involved in binding to the spike. We then combine all these interactions, showing that the interplay of all these components is critical to the behaviour of the virus. We show that the virus tropism depends on the combinatorial expression of both HS chains and receptors. Finally, we demonstrate that when both HS chains and entry receptors express at high density, steric effects dominate the interaction, preventing infection.

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Molecular modulation of calcium oxalate crystallization

AJP Renal Physiology ◽

10.1152/ajprenal.00136.2006 ◽

2006 ◽

Vol 291 (6) ◽

pp. F1123-F1132 ◽

Cited By ~ 57

Author(s):

James J. De Yoreo ◽

S. Roger Qiu ◽

John R. Hoyer

Keyword(s):

Molecular Modeling ◽

Calcium Oxalate ◽

Stone Formation ◽

Energy Levels ◽

Critical Role ◽

Specific Interactions ◽

Crystal Surfaces ◽

Site Specific

Calcium oxalate monohydrate (COM) is the primary constituent of the majority of renal stones. Osteopontin (OPN), an aspartic acid-rich urinary protein, and citrate, a much smaller molecule, are potent inhibitors of COM crystallization at levels present in normal urine. Current concepts of the role of site-specific interactions in crystallization derived from studies of biomineralization are reviewed to provide a context for understanding modulation of COM growth at a molecular level. Results from in situ atomic force microscopy (AFM) analyses of the effects of citrate and OPN on growth verified the critical role of site-specific interactions between these growth modulators and individual steps on COM crystal surfaces. Molecular modeling investigations of interactions of citrate with steps and faces on COM crystal surfaces provided links between the stereochemistry of interaction and the binding energy levels that underlie mechanisms of growth modification and changes in overall crystal morphology. The combination of in situ AFM and molecular modeling provides new knowledge that will aid rationale design of therapeutic agents for inhibition of stone formation.

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A critical role of VLA-4 in erythropoiesis in vivo

Blood ◽

10.1182/blood.v87.6.2513.bloodjournal8762513 ◽

1996 ◽

Vol 87 (6) ◽

pp. 2513-2517 ◽

Cited By ~ 54

Author(s):

K Hamamura ◽

H Matsuda ◽

Y Takeuchi ◽

S Habu ◽

H Yagita ◽

...

Keyword(s):

Monoclonal Antibody ◽

Fetal Liver ◽

Critical Role ◽

In Utero ◽

In Vitro Studies ◽

Specific Interactions ◽

Erythroid Progenitors

Hematopoiesis requires specific interactions with the microenvironments, and VLA-4 has been implicated in these interactions based on in vitro studies. To study the role of VLA-4 in hematopoiesis in vivo, we performed in utero treatment of mice with an anti-VLA-4 monoclonal antibody. Although all hematopoietic cells in fetal liver expressed VLA-4, the treatment specifically induced anemia. It had no effect on the development of nonerythroid lineage cells, including lymphoids and myeloids. In the treated liver almost no erythroblast was detected, whereas the erythroid progenitors, which give rise to erythroid colonies in vitro, were present. These results indicate that VLA-4 plays a critical role in erythropoiesis, while it is not critical in lymphopoiesis in vivo.

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Role of Heat Expansion with a Series of Ionic Liquids: The Case for Isochoric Thermoelectric Generators and Minimal Steric Repulsion

Entropy ◽

10.3390/e21111086 ◽

2019 ◽

Vol 21 (11) ◽

pp. 1086

Author(s):

Marcus Jackson ◽

Robert Engel ◽

Luat Vuong

Keyword(s):

Thermal Expansion ◽

Ionic Liquids ◽

Critical Role ◽

Intramolecular Interactions ◽

Large Temperature ◽

Thermoelectric Generators ◽

Steric Repulsion ◽

Seebeck Coefficients ◽

Heat Expansion

The role of convection in liquid thermoelectric cells may be difficult to predict because the inter- and intramolecular interactions are not currently incorporated into thermodynamic models. Here, we study the thermoelectric response of a series of five anhydrous 1-methyl-3- alkylimidazolium halide ionic liquids with varied chain length and counterion in a high-aspect-ratio, horizontal-temperature-gradient geometry, where convection is minimal. While a canonical constant-volume thermodynamic model predicts that the longer aliphatic groups exhibit larger Seebeck coefficients, we instead measure the opposite: Longer aliphatic chains correlate with lower densities and greater heat expansion, stronger intermolecular associations, stronger steric repulsion, and lower Seebeck coefficients. As evidence of the critical role of thermal expansion, we measure that the Seebeck effect is nonlinear: Values of −2.8 mV/K with a 10 K temperature difference and −1.8 mV/K with a 50 K difference are measured with ether ion. Our results indicate that steric repulsion and heat expansion are important considerations in ionic liquid design; with large temperature differences, the Seebeck coefficient correlates negatively with heat expansion. Our results suggest that Seebeck values will improve if thermal expansion is limited in a pressurized, isochoric, convection-free design.

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Characterization of Dengue Virus Complex-Specific Neutralizing Epitopes on Envelope Protein Domain III of Dengue 2 Virus

Journal of Virology ◽

10.1128/jvi.00606-08 ◽

2008 ◽

Vol 82 (17) ◽

pp. 8828-8837 ◽

Cited By ~ 122

Author(s):

Gregory D. Gromowski ◽

Nicholas D. Barrett ◽

Alan D. T. Barrett

Keyword(s):

Dengue Virus ◽

Critical Role ◽

Antigenic Site ◽

Protein Domain ◽

Virus Infectivity ◽

E Proteins ◽

Mutant Proteins ◽

Virus Complex ◽

Domain Iii

ABSTRACT The surface of the mature dengue virus (DENV) particle is covered with 180 envelope (E) proteins arranged as homodimers that lie relatively flat on the virion surface. Each monomer consists of three domains (ED1, ED2, and ED3), of which ED3 contains the critical neutralization determinant(s). In this study, a large panel of DENV-2 recombinant ED3 mutant proteins was used to physically and biologically map the epitopes of five DENV complex-specific monoclonal antibodies (MAbs). All five MAbs recognized a single antigenic site that includes residues K310, I312, P332, L389, and W391. The DENV complex antigenic site was located on an upper lateral surface of ED3 that was distinct but overlapped with a previously described DENV-2 type-specific antigenic site on ED3. The DENV complex-specific MAbs required significantly higher occupancy levels of available ED3 binding sites on the virion, compared to DENV-2 type-specific MAbs, in order to neutralize virus infectivity. Additionally, there was a great deal of variability in the neutralization efficacy of the DENV complex-specific MAbs with representative strains of the four DENVs. Overall, the differences in physical binding and potency of neutralization observed between DENV complex- and type-specific MAbs in this study demonstrate the critical role of the DENV type-specific antibodies in the neutralization of virus infectivity.

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The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

Perspectives on Language Learning and Education ◽

10.1044/lle15.2.50 ◽

2008 ◽

Vol 15 (2) ◽

pp. 50-59 ◽

Cited By ~ 1

Author(s):

Amy Philofsky

Keyword(s):

Language Development ◽

Critical Role ◽

Children With Autism ◽

Autism Spectrum ◽

Children With Asd ◽

Prevalence Estimates ◽

Notable Increase ◽

Screening Assessment ◽

Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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