A5084236065- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Toxoplasma gondii Research Studies
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Parvovirus B19 Infection Studies
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- RNA regulation and disease
- Immunotherapy and Immune Responses
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Virus-based gene therapy research
- Mosquito-borne diseases and control
- Polyomavirus and related diseases
- Adenosine and Purinergic Signaling
- Neuroscience and Neuropharmacology Research
- Signaling Pathways in Disease
- Viral Infections and Outbreaks Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune responses and vaccinations
- Neurological Complications and Syndromes
- Sperm and Testicular Function
University College London
2015-2024
The Royal Free Hospital
2013-2024
University of Cambridge
2004-2023
Centre for Immunity, Infection and Evolution
2023
Imperial College London
2022
Roland Hill (United Kingdom)
2013-2018
Addenbrooke's Hospital
2005-2014
Novartis (Switzerland)
2011
Cambridge University Press
2008
University of Wales
2007
Human cytomegalovirus (HCMV) persists as a subclinical, lifelong infection in the normal human host, but reactivation from latency immunocompromised subjects results serious disease. Latency and are defining characteristics of herpesviruses key to understanding their biology; however, precise cellular sites which HCMV is carried mechanisms regulating its during natural remain poorly understood. Here we present evidence, based entirely on direct analysis material isolated healthy virus...
Human cytomegalovirus infection perturbs multiple cellular processes that could promote the release of proapoptotic stimuli. Consequently, it encodes mechanisms to prevent cell death during infection. Using rotenone, a potent inhibitor mitochondrial enzyme complex I (reduced nicotinamide adenine dinucleotide-ubiquinone oxido-reductase), we found human protected cells from rotenone-induced apoptosis, protection mediated by 2.7-kilobase virally encoded RNA (beta2.7). During infection, beta2.7...
Human cytomegalovirus (HCMV) remains a major cause of viral disease in immunosuppressed transplant patients. The ability HCMV to establish lifelong infection humans and reactivate with devastating clinical consequences underscores the importance understanding triggers reactivation mature myeloid cells. Dendritic cell (DC) differentiation is concomitant activation cellular signaling pathways inflammatory gene expression also reactivation. Here, we show role for interleukin-6 (IL-6) through...
Significance Conventionally, vaccines are screened for induction of a neutralizing antibody response in human volunteers before proceeding to late-stage clinical trials. We present results from cytomegalovirus (HCMV) challenge study suggesting that this paradigm may not apply universally all viruses. Instead, viruses like HCMV, which establish lifelong infections and grow both cell-free cell-associated, be controlled independently potent response. Our suggest more detailed laboratory studies...
Human cytomegalovirus (HCMV) is a frequent cause of major disease following primary infection or reactivation from latency in immunocompromised patients. Infection non-permissive mononuclear cells used for analyses HCMV vitro. Using this approach, it shown here that repression lytic gene expression experimental CD34+ cells, site vivo, correlates with recruitment repressive chromatin around the immediate-early promoter (MIEP). Furthermore, long-term culture results carriage viral genomes...
Upon herpesvirus infection, viral DNA becomes associated with nuclear structures known as domain 10 (ND10). The role of ND10 during infection has long been contentious; data arguing for a in repression have countered by other showing little effect on virus infection. Here we show that knockdown human Daxx (hDaxx) expression, an important component ND10, prior to cytomegalovirus resulted increased levels immediate early RNA and protein expression this correlated association the major promoter...
Abstract Clinical and low passage strains of human CMV (HCMV) encode an additional MHC class I-related molecule UL142, in addition to the previously described UL18. The UL142 open reading frame is encoded within ULb′ region which missing from a number common high laboratory strains. Cells expressing following transfection, fibroblasts infected with recombinant adenovirus-expressing were used screen both polyclonal NK cells cell clones, completely autologous system. Analysis 100 clones...
Human cytomegalovirus (HCMV) is an opportunistic human pathogen that establishes a lifelong latent infection, which can reactivate periodically. If unchecked by robust immune response, this reactivation result in severe disease immunocompromised patients. Reactivation of virus myeloid progenitor cells concomitant with cellular differentiation through regulation the major immediate-early promoter (MIEP) chromatin remodelling. In study, we analysed expression gene transcript UL81–82as (LUNA)....
Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout host's life in a latent state with periodic episodes reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by emergence antiviral resistance absence an effective vaccine, development which is likely complicated numerous immune evasins encoded to counter adaptive responses,...
The human cytomegalovirus (HCMV) virion envelope protein glycoprotein B (gB) is essential for viral entry and represents a major target humoral responses following infection. Previously, phase 2 placebo-controlled clinical trial conducted in solid organ transplant candidates demonstrated that vaccination with gB plus MF59 adjuvant significantly increased enzyme-linked immunosorbent assay (ELISA) antibody levels whose titer correlated directly protection against posttransplant viremia. aim of...
The recent emergence of SARS-CoV-2 variants with increased transmission, pathogenesis and immune resistance has jeopardised the global response to COVID-19 pandemic. Determining fundamental biology viral understanding their evolutionary trajectories will guide current mitigation measures, future genetic surveillance vaccination strategies. Here we examine virus entry by B.1.1.7 lineage, commonly referred as UK/Kent variant. Pseudovirus infection model cell lines demonstrate that is enhanced...
The emergence of SARS-CoV-2 variants has exacerbated the COVID-19 global health crisis. Thus far, all carry mutations in spike glycoprotein, which is a critical determinant viral transmission being responsible for attachment, receptor engagement and membrane fusion, an important target immunity. Variants frequently bear truncations flexible loops N-terminal domain (NTD) spike; functional importance these modifications remained poorly characterised. We demonstrate that NTD deletions are...
Vaccination against human cytomegalovirus (CMV) infection remains high priority. A recombinant form of a protein essential for CMV entry, glycoprotein B (gB), demonstrated partial protection in clinical trial (NCT00299260) when delivered with the MF59 adjuvant. Although antibody titre gB correlated poor neutralising responses 5 known antigenic domains (AD) were evident. Here, we show that vaccination seronegative patients induces an response region term AD-6. Responses to polypeptide AD-6...
ABSTRACT The human cytomegalovirus major immediate-early protein IE86 is pivotal for coordinated regulation of viral gene expression throughout infection. A relatively promiscuous transactivator early and late transcription, also acts during infection to negatively regulate its own promoter via direct binding a 14-bp palindromic IE86-binding site, the cis repression sequence (crs), located between (MIEP) TATA box start transcription. Although such autoregulation does not involve changes in...
Human cytomegalovirus (HCMV) lytic gene expression occurs in a regulated cascade, initiated by of the viral major immediate-early (IE) proteins. Transcribed from IE promoter (MIEP), genes regulate early and late expression. This study found that substantial proportion infecting genomes became associated with histones immediately upon infection permissive fibroblasts at low m.o.i. these bore markers repressed chromatin. As progressed, however, MIEP histone marks, which correlate known...
The ability of human CMV (HCMV) to enter and establish a latent infection in myeloid cells is crucial for survival transmission the population. Initial pathogen binding entry triggers number antiviral responses, including activation proapoptotic cell death pathways, which must be countered during latency establishment. However, mechanisms responsible prosurvival state upon HCMV remain completely undefined. We hypothesized that cellular antiapoptotic machinery initially activated by promote...
The devastating clinical consequences associated with human cytomegalovirus (HCMV) infection and reactivation underscores the importance of understanding triggers HCMV in dendritic cells (DC). Here we show that ERK-mediated is dependent on mitogen stress activated kinase (MSK) family. Furthermore, this MSK mediated response CREB binding to viral major immediate early promoter (MIEP). Specifically, MIEP provides target for recruitment. Importantly, phosphorylation histone H3 required promote...