A5089334488- Hepatitis C virus research
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Liver Disease Diagnosis and Treatment
- Hepatitis B Virus Studies
- Tuberculosis Research and Epidemiology
- Systemic Lupus Erythematosus Research
- SARS-CoV-2 detection and testing
- COVID-19 epidemiological studies
- Mycobacterium research and diagnosis
- Cytokine Signaling Pathways and Interactions
- Animal Virus Infections Studies
- interferon and immune responses
- HIV/AIDS drug development and treatment
- Advanced biosensing and bioanalysis techniques
- Biomarkers in Disease Mechanisms
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Bacteriophages and microbial interactions
- Genomics and Phylogenetic Studies
- Immune cells in cancer
- Medical Research and Treatments
- Cancer Genomics and Diagnostics
- Atherosclerosis and Cardiovascular Diseases
- Viral gastroenteritis research and epidemiology
University of Glasgow
2024
MRC University of Glasgow Centre for Virus Research
2015-2022
Medical Research Council
2019-2022
Imperial College London
2013
Animal and Plant Health Agency
2012
Universidad Nacional Autónoma de México
2011
Veterinary Medicines Directorate
2010
Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability affected by the adaptive immune response but contribution of other host factors unclear. Here, we examined role played interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays crucial in spontaneous clearance or establishment chronicity following acute We performed viral genome-wide association studies using human and data from 485 patients white ancestry infected...
We have developed periscope, a tool for the detection and quantification of subgenomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation genome most open reading frames (ORFs) occurs via intermediates termed "subgenomic RNAs." sgRNAs are produced through discontinuous transcription, which relies on homology between transcription regulatory sequences (TRS-B) upstream ORF start codons that TRS-L, is located 5' UTR. TRS-L immediately preceded by leader sequence. This therefore...
Bovine tuberculosis (bTB) is a chronic disease of cattle caused by Mycobacterium bovis, member the complex group bacteria. Vaccination might offer long-term solution for controlling and priority has been given to development vaccine against bTB. Identification biomarkers in research remains elusive goal identify host correlates protection. We hypothesized that studying global gene expression we could vitro predictors protection help facilitate development. Calves were vaccinated with BCG or...
Bovine tuberculosis (bTb) remains a major and economically important disease of livestock. Improved ante-mortem diagnostic tools would help to underpin novel control strategies. The definition biomarkers correlating with progression could have impact on the rational design approaches for bTb. We used murine bTb model identify promising candidates in host transcriptome post-infection. RNA from vitro-stimulated splenocytes lung cells BALB/c mice infected aerogenically Mycobacterium bovis were...
To gain further insight into the immunopathogenesis of bovine tuberculosis (bTB), cytokine and chemokine expression cattle experimentally infected with Mycobacterium bovis was analysed in TB granulomas, using immunohistochemistry (IHC) laser capture microdissection (LCM) followed by qPCR. Immunohistochemistry conducted for cell types labelling CD68, CD3, CD4, CD8, WC1 CD79a cytokines IFN-γ, TNF-α TGF-β as well inducible form nitric oxide synthase (iNOS). qPCR mRNA TNF-α, TGF-β, IL-17A,...
Abstract Sustained viral response (SVR) rates for direct‐acting antiviral (DAA) therapy hepatitis C virus (HCV) infection routinely exceed 95%. However, a small number of patients require retreatment. Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is potent DAA combination primarily used the retreatment who failed by therapies. Here we evaluate outcomes effects resistance‐associated substitutions (RAS) in real‐world cohort, including large genotype (GT)3 infected patients. 144 from...
Sofosbuvir is a frequently used pan-genotype inhibitor of hepatitis C virus (HCV) polymerase. This drug eliminates most chronic HCV infections, and resistance-associated substitutions in the polymerase are rare. However, genotype 3 responds slightly less well to sofosbuvir-based therapies than other genotypes. We collected data from England's National Health Service Early Access Program search for factors associated with sofosbuvir treatment failure.We patient serum samples capture-fusion...
Background In the present study, we applied microarray technology to define biosignatures by transcriptome analysis in lung and spleen samples after BCG vaccination M. bovis infection of BALB/c mice. The aims were two-fold, namely that could predict vaccine success before challenge, biomarker patterns correlated with anamnestic protective responses following exposure virulent bovis. Further, these should be detectable without vitro antigenic challenge. Principal Findings After vaccination,...
Using deep sequencing technologies such as Illumina's platform, it is possible to obtain reads from the viral RNA population revealing genome diversity within a single host. A range of software tools and pipelines can transform raw into Sequence Alignment Mapping (SAM) files. We propose that interpretation should process these SAM files, directly translating individual amino acids in order extract statistics interest proportion different acid residues at specific sites. This preserves...
Abstract SARS-CoV-2, the causative agent of COVID-19, emerged in Wuhan, China December 2019 and spread rapidly throughout world. Understanding introductions this new coronavirus different settings may assist control efforts establishment frameworks to support rapid response future infectious disease outbreaks. We investigated first four weeks emergence SARS-CoV-2 virus Scotland after case reported on 1st March 2020. obtained full genome sequences from 452 individuals with a...
As antimicrobial signalling molecules, type III or lambda interferons (IFNλs) are critical for defence against infection by diverse pathogens, including bacteria, fungi and viruses. Counter-intuitively, expression of one member the family, IFNλ4, is associated with decreased clearance hepatitis C virus (HCV) in human population; contrast, a natural frameshift mutation that abrogates IFNλ4 production improves HCV clearance. To further understand how genetic variation between within species...
Abstract The second SARS virus, SARS-CoV-2, emerged in December 2019, and within a month was globally distributed. It first introduced into Scotland February 2020 associated with returning travellers visitors. By March it circulating communities across the UK, to control COVID-19 cases, prevent overwhelming of National Health Service (NHS), ‘lockdown’ on 23rd restriction people’s movements. To augment public health efforts large-scale genome epidemiology effort (as part Genomics UK (COG-UK)...
Chronic hepatitis C virus (HCV) infection of the liver with either genotype 1 or 3 gives rise to distinct pathologies, and two viral genotypes respond differently antiviral therapy.To understand these clinical differences, we compared gene transcription profiles in biopsies from patients infected gt1 gt3, uninfected controls.Gt1-infected displayed elevated levels transcripts regulated by type I III interferons (IFN), including genes that predict response IFN-α therapy. In contrast,...
Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding transmission risks in six Scottish renal dialysis units, we utilised rapid whole-genome sequencing data generated by COG-UK consortium.
SARS-CoV-2 can efficiently infect both children and adults, albeit with morbidity mortality positively associated increasing host age presence of co-morbidities. continues to adapt the human population, resulting in several variants concern (VOC) novel properties, such as Alpha Delta. However, factors driving fitness evolution paediatric cohorts remain poorly explored. Here, we provide evidence that viral co-operate shape genotypic phenotypic change primary airway cell cultures derived from...
Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) high-income where a restricted range HCV genotypes/subtypes circulate.
Abstract We have developed periscope, a tool for the detection and quantification of sub-genomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation genome most open reading frames (ORFs) occurs via intermediates termed “sub-genomic RNAs”. sgRNAs are produced through discontinuous transcription which relies on homology between regulatory sequences (TRS-B) upstream ORF start codons that TRS-L is located 5’ UTR. immediately preceded by leader sequence. This therefore found at end...
Hepatitis C virus (HCV) genotype 3 (GT-3) represents 22–30% of all infections and is the second most common among HCV genotypes. It has two main subtypes, GT-3a GT-3b, that present epidemiological differences in transmission groups. This report generated 56 64 GT-3b whole-genome sequences to conduct an evolutionary kinetics selective force analysis with reference from various countries. Evolutionary showed worldwide might have been transmitted Indian subcontinent South Asia, Europe, North...
Natural hepatitis C virus (HCV) infection is restricted to humans, whereas other primates such as rhesus macaques are non-permissive for infection. To identify human and macaque genes that differ or share the ability inhibit HCV replication, we conducted a medium-throughput screen of lentivirus-expressed host disrupt replication subgenomic replicon RNA expressing secreted Gaussia luciferase. A combined total >800 interferon-stimulated (ISGs) were screened. Our findings confirmed...
Introduction: COVID19-associated immunopathology is associated with increased production of interferon (IFN)-alpha (IFNα) and lambda3 (IFNL3). Effects IFNs are mediated by interferon-stimulated genes (ISGs) influence expression angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) SARS-CoV-2. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) via may be important vascular dysfunction hypertension. Methods: Human microvascular ECs (MEC)...