A5064213900- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- CAR-T cell therapy research
- Toxoplasma gondii Research Studies
- Immunotherapy and Immune Responses
- Poxvirus research and outbreaks
- Virus-based gene therapy research
- Reproductive System and Pregnancy
Cardiff University
2018-2023
Significance Human cytomegalovirus (HCMV) is the major infectious cause of developmental disorders in babies due to its capacity cross placenta. HCMV also a pathogen transplant recipients and HIV–AIDS patients. Despite inducing strongest immune responses observed for any human pathogen, evades host defenses persists life. Herein, we report another viral stealth strategy. UL148 reduces surface expression key cell adhesion molecule (CD58), impairing ability NK T cells be activated by...
Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence enabled by its remarkable capacity to systematically subvert host immune defenses. In exploring the finding that HCMV infection up-regulates tumor necrosis factor receptor 2 (TNFR2), ligand for pro-inflammatory antiviral cytokine TNFα, we found underlying mechanism was due targeting of protease, A Disintegrin And Metalloproteinase 17 (ADAM17). ADAM17 prototype 'sheddase', family proteases cleaves other...
Molluscum contagiosum virus (MCV) is a common cause of benign skin lesions in young children and currently the only endemic human poxvirus. Following infection primary keratinocytes epidermis, MCV induces proliferation infected cells this results production wart-like growths. Full productive observed after differentiate. During prolonged replication cycle must avoid elimination by host immune system. We therefore sought to investigate function two major histocompatibility complex...
Abstract Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence enabled by its remarkable capacity to systematically subvert host immune defences. In exploring the finding that HCMV infection upregulates tumor necrosis factor receptor 2 (TNFR2), ligand for pro-inflammatory anti-viral cytokine TNFa, we discovered underlying mechanism was due targeting of protease, A Disintegrin And Metalloproteinase 17 (ADAM17). ADAM17 prototype ‘sheddase’, family proteases cleaves...
Abstract The treatment of haematologic malignancies with adoptive cell therapy is largely limited to platforms based on patient-derived, autologous αβ T cells. Although successful, this approach comes challenges including associated toxicities, risk relapse, high production costs and a requirement gene edit cells avoid graft vs host disease (GvHD) if the be used in an allogeneic setting. In contrast cells, human Vδ1 γδ are subset defined by expression heterodimeric receptors (TCRs) composed...
Human cytomegalovirus (HCMV) is one of the most widespread, highly successful herpesviruses, establishing a life-long viral infection in humans. HCMV has been described as paradigm immune evasion able to manipulate many functions host. Here, we describe novel, post-translational mechanism which downregulates disintegrin and metalloproteinase 17 (ADAM17), ‘sheddase’ that cleaves releases over 80 membrane-anchored cytokines, cell adhesion molecules other receptors. A screen deletion mutants...
Abstract Chimeric antigen receptor (CAR) modification of αβ T cells has revolutionized the field oncology, driving focus attention to immune system target and fight malignancies. Currently available T-cell therapies come with many challenges, including alloreactivity, off-target toxicities, cytokine release syndrome, limited survival infused necessity gene edit overcome graft vs. host disease. Whilst some these limitations can be complex costly gene-engineering approaches, utilizing innate...
Abstract The recent successes of chimeric antigen receptor (CAR) T cells in the treatment hematological malignancies have led to an explosion adoptive cell therapies for cancer. Currently approved are still limited patient-autologous αβ cells. Although successful some settings, this approach comes with challenges including associated toxicities, high production costs and requirement gene edit avoid graft vs host disease allogeneic setting. In contrast cells, innate immune such as Natural...