Discovered new bird immunological pathways

A research team led by a biomedical researcher at the University of California, Riverside has discovered new immune pathways in chickens, including viruses that infect birds, humans, and animals and tend to spread diseases such as influenza and Crimea-congo bleeding. .. Fever — May be targeted.

This finding also affects diseases that affect other birds, giving greater light to the bird’s immune response to zoonotic viruses, especially how they differ from the response seen in humans. Guess.

“Understanding these differences is important for a better understanding of birds as potential reservoirs of human pathogens,” said the University of California, Riverside, which led the study published at the Frontier of Immunology. Said Scott Pegan, a professor of biomedical sciences at the Faculty of Medicine. “In addition, it allows researchers to better understand the immune pathways that may lead to effective vaccines for agricultural use in poultry.”

Birds lack a protein called ISG15 in their cells. Found in reptiles other than mammals and other birds, ISG15 helps initiate an effective immune response against viral infections. Acting as a messenger molecule, ISG15 helps stabilize host and viral proteins and regulate many antiviral responses. Instead, birds carry OASL proteins that help generate a strong immune response against viral infections. Pegan and his team focused on chicken immunity.

“We found that the chicken OASL contains features similar to those found in the mammalian ISG15,” Pegan said. “Analysis of OASL sequences from six diverse bird species indicates that these features are likely to be conserved among avian OASLs.”

The team discovered that the avian OASL has an amino acid sequence motif, LRLRGG, in what is known as the ubiquitin-like domain. This motif allows OASL to attach to other host proteins as a means of stimulating specific host antiviral pathways.

“This has never been shown,” Pegan said. “The bird’s OASL has been found to be highly functional with this unique LRLRGG motif at one end. In addition, the protein region to which this motif belongs has a 3D atomic structure similar to ISG15. This suggests that OASL plays at least part of the bird’s role that ISG15 would have played, along with discoveries related to what can be attached to the cell. ”

Pegan explained that the virus contains proteins that play two roles in suppressing the human immune system. Removes ISG15 and ubiquitin. Ubiquitin is a small protein that helps regulate the processes of other proteins in the body from host and viral proteins. Compared to these small proteins, OASL is four times larger and other regions perform different functions. Mammals have the OASL protein, but lack this additional motif for binding to other proteins, and birds may have evolved to centralize the functions performed by ISG15 and other immune pathways. It suggests that there is. This immunological pathway in birds, an alternative to ISG15, was discovered by the Pegan team.

“We now know the new immune pathways in chickens,” he said. “The virus seems to be evolutionarily tuned to try to block this pathway. With this information, rather than trying to optimize the trigger for this pathway to help chickens prevent the disease. Good vaccines and treatments can be developed, which also allow livestock programs to further enhance the potency of this pathway and result in more resistant poultry to the disease. “

reference: Shepard JD, Freitas BT, Rodriguez SE, etc.Meaning of ubiquitin-like tandem domain structure and immunomodulation in avian 2′-5’oligoadenylate synthetase-like proteins Front Imnor.. 2022; 12. Accessed on January 26, 2022. doi: doi:10.3389 / fimmu.2021.794664

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