scholarly journals Identification of plasticity and interactions of a highly conserved motif within a picornavirus capsid precursor required for virus infectivity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Thea Kristensen ◽  
Graham J. Belsham
Keyword(s):  
Virus Infectivity ◽  
Conserved Motif ◽  
Capsid Precursor

scholarly journals Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 509 ◽  
Author(s):  
Meenakshi Tiwary ◽  
Robert J. Rooney ◽  
Swantje Liedmann ◽  
Kim S. LeMessurier ◽  
Amali E. Samarasinghe
Keyword(s):  
Epithelial Cells ◽  
Influenza A Virus ◽  
Early Phase ◽  
Influenza A ◽  
Airway Epithelial Cells ◽  
Epithelial Barrier ◽  
Virus Infectivity ◽  
Airway Epithelial ◽  
In Vivo Models

Eosinophils, previously considered terminally differentiated effector cells, have multifaceted functions in tissues. We previously found that allergic mice with eosinophil-rich inflammation were protected from severe influenza and discovered specialized antiviral effector functions for eosinophils including promoting cellular immunity during influenza. In this study, we hypothesized that eosinophil responses during the early phase of influenza contribute to host protection. Using in vitro and in vivo models, we found that eosinophils were rapidly and dynamically regulated upon influenza A virus (IAV) exposure to gain migratory capabilities to traffic to lymphoid organs after pulmonary infection. Eosinophils were capable of neutralizing virus upon contact and combinations of eosinophil granule proteins reduced virus infectivity through hemagglutinin inactivation. Bi-directional crosstalk between IAV-exposed epithelial cells and eosinophils occurred after IAV infection and cross-regulation promoted barrier responses to improve antiviral defenses in airway epithelial cells. Direct interactions between eosinophils and airway epithelial cells after IAV infection prevented virus-induced cytopathology in airway epithelial cells in vitro, and eosinophil recipient IAV-infected mice also maintained normal airway epithelial cell morphology. Our data suggest that eosinophils are important in the early phase of IAV infection providing immediate protection to the epithelial barrier until adaptive immune responses are deployed during influenza.

scholarly journals D936Y and Other Mutations in the Fusion Core of the SARS-CoV-2 Spike Protein Heptad Repeat 1: Frequency, Geographical Distribution, and Structural Effect

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2622
Author(s):  
Romina Oliva ◽  
Abdul Rajjak Shaikh ◽  
Andrea Petta ◽  
Anna Vangone ◽  
Luigi Cavallo
Keyword(s):  
Three Dimensional ◽  
Salt Bridge ◽  
Structural Effect ◽  
Host Cells ◽  
Heptad Repeat ◽  
Genomic Sequences ◽  
Strong Interactions ◽  
Virus Infectivity ◽  
S Protein ◽  
Global Threat

The crown of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constituted by its spike (S) glycoprotein. S protein mediates the SARS-CoV-2 entry into the host cells. The “fusion core” of the heptad repeat 1 (HR1) on S plays a crucial role in the virus infectivity, as it is part of a key membrane fusion architecture. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On 15 February 2021, from the SARS-CoV-2 genomic sequences in the GISAID resource, we collected 415,673 complete S protein sequences and identified all the mutations occurring in the HR1 fusion core. This is a 21-residue segment, which, in the post-fusion conformation of the protein, gives many strong interactions with the heptad repeat 2, bringing viral and cellular membranes in proximity for fusion. We investigated the frequency and structural effect of novel mutations accumulated over time in such a crucial region for the virus infectivity. Three mutations were quite frequent, occurring in over 0.1% of the total sequences. These were S929T, D936Y, and S949F, all in the N-terminal half of the HR1 fusion core segment and particularly spread in Europe and USA. The most frequent of them, D936Y, was present in 17% of sequences from Finland and 12% of sequences from Sweden. In the post-fusion conformation of the unmutated S protein, D936 is involved in an inter-monomer salt bridge with R1185. We investigated the effect of the D936Y mutation on the pre-fusion and post-fusion state of the protein by using molecular dynamics, showing how it especially affects the latter one.

scholarly journals A conserved motif in human BTG1 and BTG2 proteins mediates interaction with the poly(A) binding protein PABPC1 to stimulate mRNA deadenylation

RNA Biology ◽  
2021 ◽  
pp. 1-16
Author(s):  
Hamza Amine ◽  
Nina Ripin ◽  
Sahil Sharma ◽  
Georg Stoecklin ◽  
Frédéric H Allain ◽  
...  
Keyword(s):  
Binding Protein ◽  
Conserved Motif

scholarly journals Differential Effects of Antiseptic Mouth Rinses on SARS-CoV-2 Infectivity In Vitro

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 272
Author(s):  
Chuan Xu ◽  
Annie Wang ◽  
Eileen R. Hoskin ◽  
Carla Cugini ◽  
Kenneth Markowitz ◽  
...  
Keyword(s):  
Potential Benefit ◽  
Povidone Iodine ◽  
Cellular Damage ◽  
Virus Infectivity ◽  
Viral Infectivity ◽  
Mouth Rinse ◽  
Prolonged Incubation ◽  
Differential Effects ◽  
Mouth Rinses

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) is detectable in saliva from asymptomatic individuals, suggesting a potential benefit from the use of mouth rinses to suppress viral load and reduce virus spread. Published studies on the reduction of SARS-CoV-2-induced cytotoxic effects by mouth rinses do not exclude antiseptic mouth rinse-associated cytotoxicity. Here, we determined the effect of commercially available mouth rinses and antiseptic povidone-iodine on the infectivity of replication-competent SARS-CoV-2 viruses and of pseudotyped SARS-CoV-2 viruses. We first determined the effect of mouth rinses on cell viability to ensure that antiviral activity was not a consequence of mouth rinse-induced cytotoxicity. Colgate Peroxyl (hydrogen peroxide) exhibited the most cytotoxicity, followed by povidone-iodine, chlorhexidine gluconate (CHG), and Listerine (essential oils and alcohol). The potent antiviral activities of Colgate Peroxyl mouth rinse and povidone-iodine were the consequence of rinse-mediated cellular damage when the products were present during infection. The potency of CHG was greater when the product was not washed off after virus attachment, suggesting that the prolonged effect of mouth rinses on cells impacts the antiviral outcome. To minimalize mouth rinse-associated cytotoxicity, mouth rinse was largely removed from treated viruses by centrifugation prior to infection of cells. A 5% (v/v) dilution of Colgate Peroxyl or povidone-iodine completely blocked viral infectivity. A similar 5% (v/v) dilution of Listerine or CHG had a moderate suppressive effect on the virus, but a 50% (v/v) dilution of Listerine or CHG blocked viral infectivity completely. Mouth rinses inactivated the virus without prolonged incubation. The new infectivity assay, with limited impacts of mouth rinse-associated cytotoxicity, showed the differential effects of mouth rinses on SARS-CoV-2 infection. Our results indicate that mouth rinses can significantly reduce virus infectivity, suggesting a potential benefit for reducing SARS-CoV-2 spread.

scholarly journals An Engineered Maturation Cleavage Provides a Recombinant Mimic of Foot-and-Mouth Disease Virus Capsid Assembly-Disassembly

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 500
Author(s):  
Joseph Newman ◽  
David J. Rowlands ◽  
Tobias J. Tuthill
Keyword(s):  
Capsid Protein ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Virion Assembly ◽  
Capsid Precursor ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Assembly Intermediate ◽  
Capsid Stability

Picornavirus capsids are assembled from 60 copies of a capsid precursor via a pentameric assembly intermediate or ‘pentamer’. Upon completion of virion assembly, a maturation event induces a final cleavage of the capsid precursor to create the capsid protein VP4, which is essential for capsid stability and entry into new cells. For the picornavirus foot-and-mouth disease virus (FMDV), intact capsids are temperature and acid-labile and can disassemble into pentamers. During disassembly, capsid protein VP4 is lost, presumably altering the structure and properties of the resulting pentamers. The purpose of this study was to compare the characteristics of recombinant “assembly” and “disassembly” pentamers. We generated recombinant versions of these different pentamers containing an engineered cleavage site to mimic the maturation cleavage. We compared the sedimentation and antigenic characteristics of these pentamers using sucrose density gradients and reactivity with an antibody panel. Pentamers mimicking the assembly pathway sedimented faster than those on the disassembly pathway suggesting that for FMDV, in common with other picornaviruses, assembly pentamers sediment at 14S whereas only pentamers on the disassembly pathway sediment at 12S. The reactivity with anti-VP4 antibodies was reduced for the 12S pentamers, consistent with the predicted loss of VP4. Reactivity with other antibodies was similar for both pentamers suggesting that major antigenic features may be preserved between the VP4 containing assembly pentamers and the disassembly pentamers lacking VP4.

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