A5030487152- Viral Infections and Immunology Research
- Animal Disease Management and Epidemiology
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Vector-Borne Animal Diseases
- Respiratory viral infections research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- RNA regulation and disease
- RNA Research and Splicing
- Hepatitis C virus research
- Asthma and respiratory diseases
- Parvovirus B19 Infection Studies
- Plant and Fungal Interactions Research
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Plant Virus Research Studies
- Biochemical and Structural Characterization
- Hepatitis B Virus Studies
- RNA Interference and Gene Delivery
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Respiratory and Cough-Related Research
The Pirbright Institute
2015-2025
University of Leeds
2003-2020
Institute of Structural and Molecular Biology
2009-2010
Abstract There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine SARS-CoV-2. The based on display of coronavirus spike glycoprotein receptor-binding domain (RBD) synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses RBD-SpyVLP in prime-boost regimen induce strong neutralising antibody response mice pigs that superior convalescent...
Abstract Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using single immunisation. Here, we compared immunogenicity one or two doses nCoV-19 both mice and pigs. Whilst dose induced antigen-specific antibody T cells responses, booster immunisation enhanced particularly pigs, with significant increase...
Non-enveloped viruses must deliver their viral genome across a cell membrane without the advantage of fusion. The mechanisms used to achieve this remain poorly understood. Human rhinovirus, frequent cause common cold, is non-enveloped virus picornavirus family, which includes other significant pathogens such as poliovirus and foot-and-mouth disease virus. During entry, small myristoylated capsid protein VP4 released from virus, interacts with implicated in delivery RNA into cytoplasm...
Standard methods for assessing the thermal stability of viruses can be time consuming and rather qualitative yet such data is a necessary requisite vaccine formulation. In this study novel plate-based scanning assay virus particle has been developed (PaSTRy: Particle Stability Thermal Release Assay). Two environment-sensitive fluorescent dyes, with non-overlapping emission spectra different affinities, are used to accrue simultaneously independent overall capsid, as judged by exposure...
Significance An understanding of the mechanisms by which viruses evade host immunity is essential to development antiviral drugs and viral detection strategies. Ubiquitin ubiquitin-like modifications are crucial in cellular innate immune infection responses often suppressed proteins. We here identify a previously unknown mechanism evasion. A protease, Lb pro , removes ubiquitin protein ISG15 incompletely from While this strategy efficiently irreversibly shuts down these modification systems,...
The mechanism by which poliovirus infects the cell has been characterized a combination of biochemical and structural studies, leading to working model for entry. Upon receptor binding at physiological temperature, native virus (160S) undergoes conformational change 135S particle from VP4 N terminus VP1 are externalized. These components interact with membrane proposed form pore. An additional in is accompanied release infectious viral RNA genome its delivery, presumably through pore into...
Abstract Picornaviruses are responsible for a range of human and animal diseases, but how their RNA genome is packaged remains poorly understood. A particularly studied group within this family those that lack the internal coat protein, VP4. Here we report atomic structure one such virus, Ljungan type member genus Parechovirus B, which has been linked to diabetes myocarditis in humans. The 3.78-Å resolution cryo-electron microscopy shows remarkable features, including an extended VP1 C...
Picornaviruses are important viral pathogens, but despite extensive study, the assembly process of their infectious virions is still incompletely understood, preventing development anti-viral strategies targeting this essential part life cycle. We report identification, via RNA SELEX and bioinformatics, multiple sites across genome a typical enterovirus, enterovirus-E (EV-E), that each have affinity for cognate capsid protein (CP) capsomer. Many these evolutionarily conserved known EV-E...
Equine rhinitis A virus (ERAV) is closely related to foot-and-mouth disease (FMDV), belonging the genus Aphthovirus of Picornaviridae. How picornaviruses introduce their RNA genome into cytoplasm host cell initiate replication unclear since they have no lipid envelope facilitate fusion with cellular membranes. It has been thought that dissociation FMDV particle pentameric subunits at acidic pH mechanism for release during entry, but this raises problem how transfer across endosome membrane...
ABSTRACT There is dire need for an effective and affordable vaccine against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a modular virus-like particle candidate displaying spike glycoprotein receptor-binding domain (RBD) using SpyTag/SpyCatcher technology (RBD-SpyVLP). Low doses of RBD-SpyVLP in prime-boost regimen induced strong neutralising antibody response mice pigs that was superior convalescent human sera. We evaluated quality ACE2 blocking neutralisation cell...
The assembly of foot-and-mouth disease virus (FMDV) particles is poorly understood. In addition, there are important differences in the antigenic and receptor binding properties dissociation intermediates, these also remain unexplained. We have established an experimental model which antigenicity, characteristics, vitro capsid precursor can be studied entirely from purified components. Recombinant protein (P1 region) was expressed Escherichia coli as myristoylated or unmyristoylated protein....
In common with all nonenveloped viruses, the mechanism of picornavirus membrane penetration during cell entry is poorly understood. The small, myristylated capsid protein VP4 has been implicated in this process. Here we show that recombinant human rhinovirus 16 ability to associate and induce permeability otherwise intact liposomes. This provides further evidence plays a key role entry.
The RNA genomes of picornaviruses are translated into single polyproteins which subsequently cleaved structural and non-structural protein products. For genetic economy, proteins processing intermediates have evolved to perform distinct functions. picornavirus precursor protein, P3, is produce membrane-associated 3A, primer peptide 3B, protease 3Cpro polymerase 3Dpol. Uniquely, foot-and-mouth disease virus (FMDV) encodes three similar copies 3B (3B1-3), thus providing a convenient natural...
Vaccination is important for controlling foot-and-mouth disease (FMD) in endemic regions and to lessen the effects of outbreaks FMD-free countries. The adaptation FMD virus BHK cells a necessary but time-consuming costly step vaccine production can prove problematic some isolates. Adaptation is, part, driven by receptor availability selects variants with altered specificity that result from amino acid substitutions capsid proteins. To bypass need cell culture adaptation, we generated...
Human rhinoviruses (HRV) are responsible for the majority of virus infections upper respiratory tract. Furthermore, HRV infection is associated with acute exacerbation asthma and other chronic diseases lower A small animal model HRV-induced disease required development new therapies. However, existing mouse models difficult to work until recently cell lines were thought be generally non-permissive replication in vitro. In this report we demonstrate that a minor receptor group, HRV1B, can...
Picornaviruses are non-enveloped RNA viruses that enter cells via receptor-mediated endocytosis. Because they lack an envelope, picornaviruses face the challenge of delivering their genomes across membrane endocytic vesicle into cytoplasm to initiate infection. Currently, mechanism genome release and translocation membranes remains poorly understood. Within enterovirus genus, poliovirus, rhinovirus 2, 16 have been proposed intact endosomal through virally induced pores, whereas one study has...
Recombination is one of the determinants genetic diversity in foot-and-mouth disease virus (FMDV). FMDV sequences have a mosaic structure caused by extensive intra- and inter-serotype recombination, with exception capsid-encoding region. While these genome-wide patterns broad-scale recombination are well studied, not much known about that may exist within infected hosts. In addition, detection among viruses evolving at within-host level challenging due to similarity limitations...
Viruses have evolved elaborate mechanisms to hijack the host mRNA translation machinery direct viral protein synthesis. Picornaviruses, whose RNA genomes lack a cap structure, inhibit cap-dependent translation, and utilize an internal ribosome entry site (IRES) in 5′-UTR recruit 40S ribosomal subunit. IRES activity is stimulated by set of proteins termed trans-acting factors (ITAFs). The cellular ITAF 45 (also known as PA2G4 EBP1) was identified essential for foot-and-mouth disease virus...
Aims: We examined the efficacy of tetrasodium EDTA in eradicating biofilms derived from salivary inocula or pure cultures Candida albicans on discs polymethyl methacrylate (PMMA) denture base toothbrushes that had been used normally for 4–8 weeks. Its efficiency virus neutralization was also determined. Methods and Results: Overnight (16 h) treatment with 4% (w/v) solution reduced C. biofilm viable counts by ≥99%. Biofilm removal confirmed using confocal laser scanning microscopy....