Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

A collaborative study, led by former Ludwig Oxford group leader Professor Mads Gyrd-Hansen, sheds light on the ZBP1-induced signalling pathway, a pathway which contributes to the viral immune response, including to SARS-CoV-2

A central part of the innate immune response is the detection of invading pathogens, such as viruses and bacteria, by recognition of pathogen-specific molecular markers. Nucleic acids are an example of such a marker, and are released into the host cell cytosol by invading viruses or may accumulate aberrantly in cells under stress conditions. ZBP1 is a cytosolic nucleic-acid sensing protein, which, when activated, recruits RIPK1 and RIPK3; proteins which initiate cell death as part of a wider immune response. Whilst this cell death pathway has been well characterised, a second component involving RIPK3-mediated inflammatory signalling had been suggested, although the underlying mechanisms were unknown.

In this work, Dr Ruoshi Peng and colleagues from the Gyrd-Hansen, Lu and Van den Eynde groups at Ludwig Oxford and collaborating institutes show that ZBP1 stimulates inflammatory signalling and cytokine production independently of the cell death pathway, and at a lower activation threshold. They determined that RIPK3 and RIPK1 have an essential role in this process as scaffolding proteins, acting to coordinate the response, and that a post-translational modification, ubiquitination, of this ZBP1-RIPK1-RIPK3 complex plays a key part in the proinflammatory pathway. This work suggests that ZBP1 has a dual function, inducing cell death or inflammatory signalling depending on the context.

They have also studied ZBP1’s role in the context of COVID-19. Using human lung epithelial cells, they demonstrate an upregulation of ZBP1 following SARS-CoV-2 infection, and suggest that this in turn stimulates the production of inflammatory cytokines, including CXCL10 and IL-6. This work therefore reveals a role for ZBP1 in the host response to SARS-CoV-2.

Read the full publication in EMBO reports.

Similar stories

Production of biocompatible multifunctional modular iontronics enabled by microscale droplet assembly

The Lu lab collaborates with the École Polytechnique Fédérale de Lausanne and Oxford departments to report the use of surfactant-supported assembly of freestanding microscale hydrogel droplets to construct iontronic modules and biointerfaces.