Dr Daniel Goncalves Carneiro - Imperial College London

Event details

Abstract

The recognition of nucleic acids is often the first step in establishing a protective immune response to virus infection. These responses require a finely tuned balance between responsiveness and restraint: insufficient activation permits viral replication, whereas excessive or inappropriate activation can drive inflammation and autoimmunity. A major mechanism by which cells establish this balance is through ubiquitin-mediated regulation of nucleic acid sensors. Our laboratory investigates how ubiquitin ligases regulate antiviral nucleic acid sensing and shape the outcome of virus infection. Using diverse viral models, including Enterovirus A71 and HIV-1, we combine CLIP-seq, animal models and machine-learning-based protein structure prediction to identify regulatory interactions and determine their consequences for host–virus interactions. A major focus of our work is the zinc-finger antiviral protein (ZAP), an RNA-binding antiviral protein that preferentially recognises CpG-rich regions in viral RNA, and the oligoadenylate synthetase (OAS) family of double-stranded RNA sensors. These studies reveal how ubiquitin ligases regulate the activity of antiviral proteins and thereby influence the recognition and restriction of viral pathogens. More broadly, they provide insight into the mechanisms that determine the specificity and magnitude of innate immune responses, while computational approaches are uncovering previously unrecognised connections between ubiquitin ligases and nucleic acid sensors.