Discovery of a new avian immunological pathway

A research team led by a biomedical scientist from the University of California, Riverside, has discovered a new immune pathway in chickens that viruses – such as those that tend to infect birds, humans and animals and spread diseases like influenza or Crimean-Congo hemorrhagic fever – can target.

The finding, which also has implications for diseases affecting other birds, sheds light on birds’ immune responses to zoonotic viruses – in particular, how these may differ from responses seen in humans.

“Understanding these differences is key to better understanding birds as potential reservoirs of human pathogens,” said Scott Pegan, professor of biomedical sciences at UC Riverside School of Medicine, who led the study published in Frontiers. in Immunology. “Additionally, it allows researchers to better understand the immune pathways that could lead to effective vaccines for agricultural use in poultry.”

Birds lack a protein in their cells called ISG15. Found in mammals and other non-avian reptiles, ISG15 in these species helps mount an effective immune response against viral infection. Serving as a messenger molecule, ISG15 helps stabilize host and viral proteins and regulate many antiviral responses. Instead, birds have OASL proteins that help produce a robust immune response to viral infection. Pegan and his team focused on chicken immunity.

“We found that chicken OASL contains features resembling those found in mammalian ISG15s,” Pegan said. “Our analysis of OASL sequences from six different bird species indicates that these features are likely conserved among avian OASLs.”

The team found that avian OASLs have an amino acid sequence motif, namely LRLRGG, in what is known as a ubiquitin-like domain. This motif allows OASL to bind to other host proteins to stimulate certain host antiviral pathways.

“It’s never been shown before,” Pegan said. “We found that OASL in birds had this unique LRLRGG motif at one end and it was very functional. Additionally, the region of the protein to which this motif belongs has a 3D atomic structure similar to ISG15. This , along with findings related to what it can attach inside cells, suggests that OASL plays at least part of the role in birds that ISG15 would have played.

Pegan explained that to suppress the human immune system, a virus contains a protein that performs two functions: eliminating ISG15 as well as ubiquitin, a small protein that helps regulate the processes of other proteins in the body from host and viral proteins. Compared to these small proteins, OASLs are four times larger and with other areas performing different functions. Although mammals have OASL proteins, they lack this additional motive to conjugate with other proteins, suggesting that birds may have evolved to centralize the functions performed by ISG15 and other immune pathways. This immunological pathway in birds, which overrides ISG15, is what Pegan’s team discovered.

“We now know of a new immune pathway in chickens,” he said. “Viruses appear to be evolving to try to interfere with this pathway. This information allows us to develop better vaccines and treatments that seek to optimize the firing of this pathway to help chickens avoid disease. to further improve the potency of this pathway leading to more disease resistant poultry.

Reference: Shepard JD, Freitas BT, Rodriguez SE, et al. The structure and immune regulatory implications of the ubiquitin-like tandem domain in an avian 2′-5′ oligoadenylate synthetase protein. Immunol before. 2022;12. Accessed January 26, 2022. doi:10.3389/fimmu.2021.794664

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