A5062152339- Hepatitis C virus research
- Hepatitis B Virus Studies
- Liver Disease Diagnosis and Treatment
- interferon and immune responses
- Herpesvirus Infections and Treatments
- Systemic Lupus Erythematosus Research
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Virus-based gene therapy research
- Lipid metabolism and biosynthesis
- SARS-CoV-2 and COVID-19 Research
- Cytomegalovirus and herpesvirus research
- Endoplasmic Reticulum Stress and Disease
- Cytokine Signaling Pathways and Interactions
- Viral Infections and Immunology Research
- Animal Virus Infections Studies
- Monoclonal and Polyclonal Antibodies Research
- Atherosclerosis and Cardiovascular Diseases
- Inflammasome and immune disorders
- Bacteriophages and microbial interactions
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- Biomarkers in Disease Mechanisms
- Mosquito-borne diseases and control
- Alcohol Consumption and Health Effects
MRC University of Glasgow Centre for Virus Research
2015-2025
Medical Research Council
1992-2025
University of Glasgow
2000-2024
University of Liverpool
2024
International Severe Acute Respiratory and Emerging Infection Consortium
2023
Guangzhou Blood Center
2022
University of Nottingham
2021
Queen's Medical Centre
2021
International Centre for Genetic Engineering and Biotechnology
2017
University of Southampton
2015
Journal Article The consensus sequence YGTGTTYY located downstream from the AATAAA signal is required for efficient formation of mRNA 3′ termini Get access John McLauchlan, McLauchlan MRC Virology Unit, Insitute VirologyChurch Street, G1asgow G11 5JR, UK Search other works by this author on: Oxford Academic PubMed Google Scholar Dairena Gaffney, Gaffney J.Lindsay Whitton, Whitton J.Barklie Clements * To whom correspondence should be addressed Nucleic Acids Research, Volume 13, Issue 4, 25...
The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus Flaviviridae family into major public health concern. Little is currently known about evolution and biology ZIKV factors that contribute to associated pathogenesis. Determining genomic sequences clinical viral isolates characterization elements within these are an important prerequisite advance our understanding replicative processes virus-host interactions.We obtained...
In infected cells, hepatitis C virus (HCV) core protein is targeted to lipid droplets, which serve as intracellular storage organelles. Using a tissue culture system generate infectious HCV, we have shown that the coating of droplets by occurs in time-dependent manner and coincides with higher rates production. At earlier times, was located at punctate sites close proximity edge droplets. Investigations using Z-stack analysis many contained single site could represent positions where...
Chronic hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. Restriction HCV to human hepatocytes suggests that liver-specific host factors play role in the viral life cycle. Using yeast-two-hybrid system, we identified apolipoprotein E (apoE) as liver-derived factor specifically interacting with nonstructural protein 5A (NS5A) but not other proteins. The relevance apoE–NS5A interaction for was confirmed by co-immunoprecipitation and co-localization studies apoE...
Attachment of hepatitis C virus (HCV) core protein to lipid droplets (LDs) is linked release infectious progeny from infected cells. Core progressively coats the entire LD surface a unique site on organelle, and this process coincides with aggregation around nucleus. We demonstrate that redistribution requires only accompanied by reduced abundance adipocyte differentiation-related (ADRP) surfaces. Using small hairpin RNA technology, we show knock down ADRP has similar phenotypic effect...
From analysis of the primary sequence hepatitis C virus (HCV) core protein, we have identified three separable regions based on hydrophobicity and clustering basic amino acids within protein. Comparison with capsid proteins related pesti- flaviviruses suggested that HCV has a unique central domain (domain 2). Previous findings revealed protein can associate lipid droplets which are intracellular storage sites for triacylglycerols cholesterol esters. Confocal variant forms lacking indicated...
Neutral lipid is stored in spherical organelles called droplets that are bounded by a coat of proteins. The protein most frequently found at the surface adipocyte differentiation-related (ADRP). In this study, we demonstrate fusion either human or mouse ADRP coding sequences to green fluorescent (GFP) does not disrupt ability associate with droplets. Using system identify targeting elements, discontinuous segments within region were required for directing GFP-tagged was employed also examine...
The mechanisms involved in hepatitis C virus (HCV) RNA replication are unknown, and this aspect of the life cycle is not understood. It thought that virus-encoded nonstructural proteins genomes interact on rearranged endoplasmic reticulum (ER) membranes to form complexes, which believed be sites synthesis. We report that, through use an antibody specific for double-stranded (dsRNA), dsRNA readily detectable Huh-7 cells contain replicating HCV JFH-1 but absent control cells. Therefore, as...
It is currently believed that type I and III interferons (IFNs) have redundant functions. However, the preferential distribution of IFN receptor on epithelial cells suggests functional differences at surfaces. Here, using human intestinal we could show although both IFNs confer an antiviral state to cells, they do so with distinct kinetics. Type signaling characterized by acute strong induction interferon stimulated genes (ISGs) confers fast protection. On contrary, slow acting mediated...
Virus genome sequences, generated in ever-higher volumes, can provide new scientific insights and inform our responses to epidemics outbreaks. To facilitate interpretation, such data must be organised processed within scalable computing resources that encapsulate virology expertise. GLUE (Genes Linked by Underlying Evolution) is a data-centric bioinformatics environment for building resources. The core schema organises sequence along evolutionary lines, capturing not only nucleotide but...
A modular system for assaying the activity of transcriptional regulatory signals based on herpes simplex virus (HSV) promoter and terminator sequences linked to bacterial chloramphenicol acetyltransferase (CAT) gene has been used study activation HSV immediate early (IE) expression. Insertion SV40 72 base pair (bp) repeat increased mRNA levels by 15-fold thus demonstrating ability IE respond a heterologous enhancer. fragment containing part intergenic region located between HSV-2 genes-3...
We have shown previously that a novel herpes simplex virus-induced activity, LPF, selectively increases RNA 3'-end processing at the poly(A) site of late virus gene (J. McLauchlan, S. Simpson, and J. B. Clements, Cell 59:1093-1105, 1989). Here, our in vivo vitro analyses both demonstrate LPF is induced during early stages infection. Studies mutants indicate expression immediate-early IE63 required for induction this activity. The selective effects on 3' displayed presence provide direct...
The cellular DEAD-box protein DDX3 was recently shown to be essential for hepatitis C virus (HCV) replication. Prior that, we had reported that HCV core binds in yeast-two hybrid and transient transfection assays. Here, confirm by co-immunoprecipitation this interaction occurs cells replicating the JFH1 virus. Consistent with result, immunofluorescence staining of infected revealed a dramatic redistribution cytoplasmic assembly sites around lipid droplets. Given close association droplets,...
Complete maturation of hepatitis C virus (HCV) core protein requires coordinate cleavage by signal peptidase and an intramembrane protease, peptide peptidase. We show that reducing the intracellular levels lowers titer infectious released from cells, indicating it plays important role in production. Proteolysis enzyme at a between E1 glycoprotein is needed to permit targeting lipid droplets. From mutagenesis studies, introducing mutations into core-E1 delayed appearance peptidase-processed...
We have determined the orientation of 4 immediate early (IE) mRNA's on herpes simplex virus type 1 genome by mapping cDNA's complementary to 3'-termini messages. These IE are transcribed a pre-existing cell RNA polymerase, and we propose model which allows their synthesis from circular template using single promoter region. The region, is located in two repetitive DNA regions flank short unique region genome, may serve initiate bidirectional transcription these mRNA's.
Early events leading to the establishment of hepatitis C virus (HCV) infection are not completely understood. We show that intact and dynamic microtubules play a key role in initiation productive HCV infection. Microtubules were required for entry into cells, as evidenced using pseudotypes presenting envelope proteins on their surface. Studies carried out recent infectious model revealed also an essential early, postfusion steps cycle. Moreover, low concentrations vinblastin nocodazol,...
ABSTRACT Type I interferon (IFN) signalling induces the expression of several hundred IFN‐stimulated genes (ISGs) that provide an unfavourable environment for viral replication. To prevent overexuberant response and autoinflammatory disease, IFN requires tight control. One critical regulator is ubiquitin‐like protein gene 15 (ISG15), evidenced by disease in patients with inherited ISG15 deficiencies. Current models suggest stabilises ubiquitin‐specific peptidase 18 (USP18), a...