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Pirbright first to characterise chicken proteins thought to cause immune exhaustion

An overlay of the structures of chicken PD-L1 (yellow) with human PD-L1 (red).

Two chicken proteins that may be involved in immune regulation of cancerous cells and viral infection, named Programmed death 1 (PD-1) and Programmed death ligand 1 (PD-L1), have been characterised for the first time by scientists at the BBSRC-funded Pirbright Institute. The results are published In a study for Frontiers in Cellular and Infection Microbiology.

They demonstrated that the protein structures and interactions were highly similar to those in humans and other animals, where activation of these proteins is known to cause immune cell ‘exhaustion’ and prevent the immune system from destroying infected cells. Their work will provide the basis for the development of immunotherapy treatments that block the pathway, which could revive immune cells and enable them to clear infection.

 “Demonstrating that this pathway exists in birds will help us to establish how the poultry immune response deals with viral infections”, said Professor Venu Nair, Head of the Viral Oncogenesis group. “We are confident that the similarity of chPD-1 and chPD-L1 proteins to those in other species means that they are also involved in suppressing the poultry immune system.”

“Our next steps will be to investigate the role of chPD-1 and chPD-L1 pathways during infection and how viruses such as Marek’s disease virus manipulate the pathway to evade destruction, allowing the virus to remain latent in the infected cell and cause diseases such as cancer. This could help us to create immunotherapies that revive T cells from their exhausted state and allow them to deal with infection. Although the antibodies we created did not prevent interaction between chPD-1 and chPD-L1, we hope further research will result in antibodies that block this pathway and can help to alleviate economically important poultry diseases” added Professor Nair.

Full Pirbright Institute press release here:

This research was supported by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI), and the Royal Society International Collaboration Award for Research Professors.

Tags: viral infections chickens poultry pirbright