New research uncovers infection mechanism behind deadly disease in cattle

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Researchers from the University of Liège (ULiège) in Liège, Belgium, have published a study that amplifies existing knowledge on malignant catarrhal fever (MCF), a highly lethal and infectious peripheral T cell lymphoma that affects ruminants.^1,2 The disease has become a serious threat to the commercial bison industry in the past few years, and continues to be a significant problem in farmed deer operation.² The recent study delves deeper into what causes cattle to develop MCF.

MCF primarily affects farm animals like domestic cattle, water buffalos, Bali cattle, American bison, and deer. Occasionally, but rarely, it affects swine, and has been recorded in captive ruminants within diverse zoological collections. It is a systemic lymphoproliferative disease of artiodactyls that is caused by alcelaphine gammaherpesvirus 1 (AlHV-1)—a ruminant virus. Usually fatal, the disease is especially lethal in species like bison and certain deer species, with it being capable of infecting extensive animal populations. In cattle, however, MCF tends to occur sporadically and generally only affects single animals. Primary carriers of MCF are wildebeest and domestic sheep, which are asymptomatic to the virus.²

In 2013, researchers from the same university published a study that revealed that MCF only develops if the AlHV-1 virus can maintain a latent state of replicating its viral genome in CD8+ T lymphocytes without generating viral particles. In the recent study, published on August 1, 2024, the ULiège research team found that the AIHV-1 virus leads to major transcriptomic and epigenomic changes in CD8+T lymphocytes in cattle. Specifically, an AIHV-1 infection causes an oligoclonal expansion of these CD8+T cells.^1,3

“In this new study, we used high-throughput sequencing approaches on CD8+ T lymphocytes from sick cattle, compared with healthy animals," Benjamin Dewals, researcher at Fundamental and Applied Research for Animals and Health Research Unit (FARAH) and professor in the department of Infectious and Parasitic Diseases at the Faculty of Veterinary Medicine at ULiège, said in a news release.¹ “We were able to characterize the T lymphocyte repertoire [TCR sequencing] as well as the expression of cellular and viral genes specifically regulated during infection.”

From the sequencing, researchers found A10, a viral gene coding for a protein, which shows involvement in the intracellular signaling of infected cells, according to the news release. “This protein turned out to be essential for the development of the disease without affecting viral replication in cell culture", Meijiao Gong, PhD student at ULiège and co-author of the article, explained in the release.¹ “In addition, we have shown that phosphorylation of A10 alters the phenotype of T lymphocytes, causing their proliferation and the development of MCF."

The results from the study offer a detailed account of how CD8+ T cells are reprogrammed during an AlHV-1 infection. The research also identifies A10 as an essential factor in MCF development. These findings not only develop existing knowledge on how herpesviruses induce malignant lymphoproliferation, but allows for new perspectives surrounding its infection mechanism, according to ULiège.¹

The findings of the research also have further implications for the protection of cattle health. "This study represents a significant step forward in our understanding of malignant catarrhal fever and offers hope for the development of a vaccine capable of protecting cattle against this devastating disease," Dewals said in the release.¹

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References

1. New progress in research into malignant catarrhal fever in cattle. News release. Liège Université. July 29, 2024. Accessed August 8, 2024. https://www.news.uliege.be/cms/c_19842709/en/new-progress-in-research-into-malignant-catarrhal-fever-in-cattle
2. Lear AS. Malignant catarrhal fever in animals. Merck Veterinary Manual. February 2022. Accessed August 8 2024. https://www.merckvetmanual.com/generalized-conditions/malignant-catarrhal-fever/malignant-catarrhal-fever-in-animals
3. Gong M, Myster F, Azouz A, et al. Unraveling Clonal CD8 T cell expansion and identification of essential factors in γ-herpesvirus-induced lymphomagenesis. Proceedings of the National Academy of Sciences. 2024;121(32). https://doi.org/10.1073/pnas.2404536121