A5057671161- Influenza Virus Research Studies
- Animal Disease Management and Epidemiology
- interferon and immune responses
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- Viral Infections and Vectors
- Herpesvirus Infections and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Immune Response and Inflammation
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
- Sulfur Compounds in Biology
- Animal Genetics and Reproduction
- Virology and Viral Diseases
- Adipose Tissue and Metabolism
- Virus-based gene therapy research
- Biochemical effects in animals
- Vector-Borne Animal Diseases
- RNA Research and Splicing
MRC University of Glasgow Centre for Virus Research
2018-2024
Medical Research Council
2021
Roslin Institute
2013-2019
University of Edinburgh
2013-2019
The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention SARS-CoV-2, meaning there is an urgent need for tools that can be used in unaccustomed working with coronaviruses. Here we report range SARS-CoV-2 research. First, describe facile single plasmid reverse...
Inherited genetic factors can influence the severity of COVID-19, but molecular explanation underpinning a association is often unclear. Intracellular antiviral defenses inhibit replication viruses and reduce disease severity. To better understand relevant to we used interferon-stimulated gene (ISG) expression screening reveal that 2′-5′-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show common...
Remdesivir (RDV), a broadly acting nucleoside analogue, is the only FDA approved small molecule antiviral for treatment of COVID-19 patients. To date, there are no reports identifying SARS-CoV-2 RDV resistance in patients, animal models or vitro. Here, we selected drug-resistant viral populations by serially passaging vitro presence RDV. Using high throughput sequencing, identified single mutation RNA-dependent RNA polymerase (NSP12) at residue conserved among all coronaviruses two...
Bunyaviruses pose a significant threat to human health, prosperity, and food security. In response viral infections, interferons (IFNs) upregulate the expression of hundreds interferon-stimulated genes (ISGs), whose cumulative action can potently inhibit replication bunyaviruses. We used flow cytometry-based method screen ability ∼500 unique ISGs from humans rhesus macaques Bunyamwera orthobunyavirus (BUNV), prototype both Peribunyaviridae family Bunyavirales order. Candidates possessing...
COVID-19 is caused by a novel coronavirus called severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Virus cell entry mediated through protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and angiotensin-converting enzyme (ACE2). A series of stapled peptide ACE2 peptidomimetics based on motif were designed to bind S-protein RBD inhibit binding human receptor. The assessed for antiviral activity in an array assays including neutralization pseudovirus assay,...
Interferons (IFN) are cytokines that regulate the expression of hundreds genes during viral infections to generate a broadly antiviral environment in stimulated cell. Antiviral breadth is provided by concurrent many individual IFN-stimulated (ISG), each encoding protein with often exquisite specificity. can also be encoded at single genetic loci ISG products detect molecular feature common diverse types viruses, such as RNA or lipid envelope. Here, we show mechanistic plasticity locus novel...
The global market for protein drugs has the highest compound annual growth rate of any pharmaceutical class but their availability, especially outside US market, is compromised by high cost manufacture and validation compared to traditional chemical drugs. Improvements in transgenic technologies allow valuable proteins be produced genetically-modified animals; several therapeutic from such animal bioreactors are already on after successful clinical trials regulatory approval. Chickens have...
Vesicular stomatitis Indiana virus (VSIV), formerly known as vesicular (VSV) (VSV
Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy while sparing the mRNAs that encode antiviral effectors. Here, we show highly upregulated interferon-stimulated genes (ISGs), which proteins, have distinctive nucleotide compositions. We propose self-targeting by effectors has selected ISG transcripts occupy less self-targeted sequence space. Following interferon (IFN) stimulation, CpG-targeting effector...
ABSTRACT Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The allele is found avian and mammalian viruses, but the B viewed as being almost exclusively This might reflect fact that one or both its encoded proteins (NS1 NEP) are maladapted for replication hosts. To test this, a number clade virus-derived NS segments were introduced into human H1N1 H3N2 In no case was peak virus titer substantially reduced following infection various cell types. Exemplar...
Abstract Remdesivir (RDV) is used widely for COVID-19 patients despite varying results in recent clinical trials. Here, we show how serially passaging SARS-CoV-2 vitro the presence of RDV selected drug-resistant viral populations. We determined that E802D mutation RNA-dependent RNA polymerase was sufficient to confer decreased sensitivity without affecting fitness. Analysis more than 200,000 sequences globally circulating variants no evidence widespread transmission RDV-resistant mutants....
Influenza A virus is a widespread pathogen that affects both humans and variety of animal species, causing regular epidemics sporadic pandemics, with major public health economic consequences. better understanding biology therefore important. The primary control measure vaccination, which for mostly relies on antigens produced in eggs from PR8-based viruses bearing the glycoprotein genes interest. However, not all reassortants replicate well enough to supply sufficient antigen demand....
Background Many human strains of influenza A virus produce highly pleomorphic particles that at the extremes can be approximated as either spheres around 100 nm diameter or filaments similar cross-section but elongated to lengths many microns. The role filamentous virions play in life cycle remains enigmatic. Objectives/Methods Here, we set out define morphology and genetics particle shape equine virus, using reverse microscopy infected cells. Results Conclusions majority H3N8 tested were...
Abstract Cross-species transmission of avian influenza A viruses (IAVs) into humans could represent the first step a future pandemic 1 . Multiple factors limiting spillover and adaptation IAVs in have been identified, but they are not sufficient to explain which virus lineages more likely cross species barrier 1,2 Here, we identified human BTN3A3 3 (butyrophilin subfamily member A3) as potent inhibitor IAVs. We determined that is constitutively expressed airways its antiviral activity...
Candidate vaccine viruses (CVVs) for seasonal influenza A virus are made by reassortment of the antigenic with an egg-adapted strain, typically A/Puerto Rico/8/34 (PR8). Many 2009 A(H1N1) pandemic (pdm09) high-growth reassortants (HGRs) selected this way contain pdm09 segment 2 in addition to genes. To investigate this, we CVV mimics reverse genetics (RG) that were either 6 : or 5 3 between PR8 and two strains, A/California/7/2009 (Cal7) A/England/195/2009, differing source 2. The replicated...
Abstract Cell autonomous antiviral defenses can inhibit the replication of viruses and reduce transmission disease severity. To better understand response to SARS-CoV-2, we used interferon-stimulated gene (ISG) expression screening reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show while some people express a prenylated OAS1 variant, is membrane-associated blocks SARS-CoV-2 infection, other cytosolic, nonprenylated variant which does not detect (determined by...
H5N1 avian influenza virus (lineage 2.3.4.4b, B3.13 genotype) has caused, unexpectedly, a large outbreak in dairy cattle North America. It is critical to ascertain how this specifically adapted bovine cells and the molecular determinants of process. Here, we focused on contribution viral internal genomic segments adaptation. We generated 45 reassortant viruses harbouring haemagglutinin neuraminidase from A/Puerto Rico/8/1934 gene constellations several A (IAV) or carrying segment swaps...
Abstract The PA-X protein of influenza A virus has roles in host cell shut-off and viral pathogenesis. While most strains are predicted to encode PA-X, strain-dependent variations activity have been noted. We found that from A/PR/8/34 (PR8) strain had significantly lower repressive against cellular gene expression compared with PA-Xs the avian A/turkey/England/50-92/91 (H5N1) (T/E) A/chicken/Rostock/34 (H7N1). Loss normal expression, either by mutation frameshift site or truncating X-ORF,...
ABSTRACT Vesicular Stomatitis Indiana Virus (VSIV) is a model virus that exceptionally sensitive to the inhibitory action of interferons. Interferons induce an antiviral state by stimulating expression hundreds interferon stimulated genes (ISGs). These ISGs constrain viral replication, limit tissue tropism, reduce pathogenicity and inhibit transmission. Because VSIV used as backbone for multiple oncolytic vaccine strategies, understanding how restrict VSIV, not only helps in...
Abstract Candidate vaccine viruses (CVVs) for seasonal influenza A virus are made by reassortment of the antigenic with a high-yielding egg-adapted strain, typically A/Puerto Rico/8/34 (PR8). Many 2009 H1N1 pandemic (pdm09) high-growth reassortants (HGRs) selected this process contain pdm09 segment 2 in addition to genes. To investigate this, we CVV mimics reverse genetics (RG) that were either 6:2 or 5:3 between PR8 and two strains, A/California/7/2009 (Cal7) A/England/195/2009, differing...