A5048080277- interferon and immune responses
- Virology and Viral Diseases
- Viral Infections and Vectors
- Animal Disease Management and Epidemiology
- Viral Infections and Immunology Research
- Vector-Borne Animal Diseases
- Animal Virus Infections Studies
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Cytokine Signaling Pathways and Interactions
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Research on Leishmaniasis Studies
- Plant Virus Research Studies
- Immune Response and Inflammation
- Genomics and Rare Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Multiple Myeloma Research and Treatments
- Herpesvirus Infections and Treatments
- Polyomavirus and related diseases
- Genetics and Neurodevelopmental Disorders
The Pirbright Institute
2021-2023
St George's, University of London
2003-2018
University of London
2003-2005
University of St Andrews
2004-2005
St George's Hospital
2005
University of Sheffield
2002
Cancer Research UK
2002
The Christie Hospital
2002
Most paramyxoviruses circumvent the IFN response by blocking signaling and limiting production of virus-infected cells. Here we report that highly conserved cysteine-rich C-terminal domain V proteins a wide variety binds melanoma differentiation-associated gene 5 (mda-5) product. mda-5 is an IFN-inducible host cell DExD/H box helicase contains caspase recruitment at its N terminus. Overexpression stimulated basal activity IFN- β promoter in reporter assays significantly enhanced activation...
RIG-I and mda-5 are activated by viral RNA stimulate type I interferon production. Laboratory of genetics physiology 2 (LGP2) shares homology with but lacks the CARD domains required for signaling. The V proteins paramyxoviruses limit induction binding preventing its activation; however, they do not bind have been considered inhibitors Here we uncover a novel mechanism inhibition in which protein parainfluenzavirus 5 (PIV5; formerly known as simian virus [SV5]) interacts LGP2 cooperatively...
The RNA helicases encoded by melanoma differentiation-associated gene 5 (mda-5) and retinoic acid-inducible I (RIG-I) detect foreign cytoplasmic molecules generated during the course of a virus infection, their activation leads to induction type interferon synthesis. Paramyxoviruses limit amount produced infected cells through action V protein, which binds inhibits mda-5. Here we show that both mda-5 RIG-I double-stranded (dsRNA) formation homo-oligomers self-association helicase domains. We...
ABSTRACT The African swine fever virus (ASFV) DP71L protein is present in all isolates as either a short form of 70 to 72 amino acids or long about 184 acids, and both these share sequence similarity the C-terminal domain herpes simplex ICP34.5 cellular GADD34. In study we expressed different mammalian cells demonstrated that causes dephosphorylation eukaryotic translation initiation factor 2 alpha (eIF2α) resting during chemical-induced endoplasmic reticulum stress acts enhance expression...
The DExD/H box RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (mda-5) sense viral in the cytoplasm of infected cells activate signal transduction pathways that trigger production type I interferons (IFNs). Laboratory genetics physiology 2 (LGP2) is thought to influence IFN by regulating activity RIG-I mda-5, although its mechanism action not known function controversial. Here we show expression LGP2 potentiates induction...
We have identified two novel proteins that interact specifically with the C‐terminal repression domain of Interferon Regulatory Factor‐2 (IRF‐2). These proteins, which we term IRF‐2 binding 1 and 2 (IRF‐2BP1 IRF‐2BP2, latter having splicing isoforms, A B), are nuclear properties IRF‐2‐dependent transcriptional co‐repressors can inhibit both enhancer‐activated basal transcription in a manner is not dependent upon histone deacetylation. IRF‐2BP1 IRF‐2BP2A/B contain an N‐terminal zinc finger...
The V protein of simian virus 5 (SV5) facilitates the ubiquitination and subsequent proteasome-mediated degradation STAT1. Here we show, by visualizing direct protein-protein interactions using yeast two-hybrid system, that while SV5 fails to bind STAT1 directly, it binds directly independently both DDB1 STAT2, two cellular proteins known be essential for SV5-mediated We also demonstrate STAT2 interact show acts as an adaptor molecule linking STAT2/STAT1 heterodimers, which in presence...
Abstract Childhood onset clinical syndromes involving intellectual disability and dysmorphic features, such as polydactyly, suggest common developmental pathways link seemingly unrelated phenotypes. We identified a consanguineous family of Saudi origin with varying complex features including disability, speech delay, facial dysmorphism polydactyly. Combining, microarray based comparative genomic hybridisation (CGH) to identify regions homozygosity, exome sequencing, led the identification...
Type I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression neighboring suppress replication. III IFNs have similar properties, however their effects limited epithelial at mucosal surfaces due restricted the type IFN receptor. Rotavirus (RV) replicates intestinal that respond predominantly IFNs, it has been shown rather than important for controlling RV infections vivo. The NSP1 protein antagonizes host targeting...
Mapuera virus (MPRV) is a paramyxovirus that was originally isolated from bats, but its host range remains unknown. It classified as member of the genus Rubulavirus on basis structural and genetic features. Like other rubulaviruses it encodes V protein (MPRV/V) functions an interferon (IFN) antagonist. Here we show MPRV/V differs IFN antagonists in does not induce proteasomal degradation STAT proteins, key factors signalling cascade. Rather, prevents nuclear translocation STATs response to...
Foot-and-mouth disease (FMD) is endemic in large parts of sub-Saharan Africa, Asia and South America, where outbreaks cloven-hooved livestock threaten food security have severe economic impacts. Vaccination regions remains the most effective control strategy. Current FMD vaccines are produced from chemically inactivated foot-and-mouth virus (FMDV) grown suspension cultures baby hamster kidney 21 cells (BHK-21). Strain diversity means one subtype may not fully protect against circulating...
Foot-and-mouth disease is an economically devastating of livestock caused by foot-and-mouth virus (FMDV). Vaccination the most effective control measure in place to limit spread disease; however, success vaccination campaigns hampered antigenic diversity FMDV and rapid rate at which new strains emerge that escape pre-existing immunity. has seven distinct serotypes, within each serotype are multiple often induce little cross-protective The a consequence high error RNA-dependent RNA...
Foot-and-mouth disease (FMD) is a highly contagious viral of livestock which prevalent across Africa, the Middle East, Asia, and South America where it has severe economic impact on agriculture industry. Vaccination with inactivated vaccines used as main control measure in these endemic regions world, however presence multiple serotypes, subtypes, continual emergence new, antigenically divergent strains limits its effectiveness. East Africa (EA) been identified region that would particularly...
Porcine reproductive and respiratory syndrome viruses (PRRSV-1 -2) are the causative agents of one most important infectious diseases affecting global pig industry. Previous studies, largely focused on PRRSV-2, have shown that non-structural protein-1α (NSP1α) NSP1β modulate host cell responses; however, underlying molecular mechanisms remain to be fully elucidated. Therefore, we aimed identify novel PRRSV-1 NSP1–host protein interactions improve our knowledge NSP1-mediated immunomodulation....
Foot-and-mouth disease, caused by foot-and-mouth disease virus (FMDV), is an economically devastating affecting several important livestock species. FMDV antigenically diverse and exists as seven serotypes comprised of many strains which are poorly cross-neutralised antibodies induced infection or vaccination. Co-infection recombination drivers antigenic diversity, especially in regions where co-circulate at high prevalence, therefore experimental systems to study these events vitro would be...
Porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) causes huge economic losses to the European pig industry. PRRSV-1 is divided into 3 subtypes exhibits considerable antigenic heterogeneity. Due its high mutation rate, constantly evolving, highly virulent, particularly subtype strains, are continually emerging. The mechanism(s) underlying virulence have not been fully elucidated. In vivo studies implicated replication kinetics, cell tropism an enhanced pro-inflammatory cytokine...
0.33lM (+/-0.13lM) in a cell-free assay 1 .RHPS4 is novel pentacyclic acridine (3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulphate) synthesised at Nottingham.The aims of the study were to investigate pharmaceutical and biological properties RHPS4 assess whether it was suitable drug for further development validate telomerase inhibitory effects by pre-clinical, vitro stage.RHPS4 has been shown possess convenient properties: high aqueous solubility (>5mg/ml) determined...