Deletion of H108R reduces virulence of the Georgia strain of African swine fever virus with surviving animals being protected against virulent challenge

Authors: VUONO, ELIZABETH - University Of Wisconsin; Ramirez-Medina, Elizabeth; Silva, Ediane; RAI, AYUSHI - Oak Ridge Institute For Science And Education (ORISE); Pruitt, Sarah; Espinoza, Nallely; VALLADARES, ALYSSA - Oak Ridge Institute For Science And Education (ORISE); Velazquez, Lauro; Gladue, Douglas; Borca, Manuel

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2022
Publication Date: 7/6/2022
Citation: Vuono, E., Ramirez Medina, E., Silva, E.B., Rai, A., Pruitt, S.E., Espinoza, N.N., Valladares, A., Velazquez Salinas, L., Gladue, D.P., Borca, M.V. 2022. Deletion of H108R reduces virulence of the Georgia strain of African swine fever virus with surviving animals being protected against virulent challenge. Journal of Virology. https://doi.org/10.1128/jvi.00545-22.
DOI: https://doi.org/10.1128/jvi.00545-22

Interpretive Summary: African swine fever virus (ASFV) causes a devastating disease in swine, called African swine fever (ASF), that is currently spreading across Europe and Asia. There is no available vaccine for ASF, and currently only experimental live attenuated vaccines are derived from deletions of individual genes in the ASFV genome. In this study we were able to delete a a new protein and able to partially attenuate the virus.

Technical Abstract: African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF) a devastating disease affecting domestic and wild swine, currently causing a global pandemic severely affecting swine production. Here, we demonstrate that deletion of the previously uncharacterized ASFV gene H108R, from highly virulent ASFV-Georgia2010 (ASFV-G) strain reduces virulence in domestic swine. ASFV-G-'H108R, a recombinant virus with H108R deleted, was used to evaluate the involvement of H108R for ASFV replication and virulence in swine. ASFV-G-'H108R showed a delayed replication in swine macrophages cultures. A group of five pigs, intramuscularly inoculated with 102 HAD50 of ASFV-G-'H108R, was observed during a 28 day period and compared with a similar group of animals inoculated with similar dose of the parental virulent virus. While all animals inoculated with ASFV-G developed an acute fatal disease, ASFV-G-'H108R inoculated animals, with the exception of one animal showing a protracted but fatal form of the disease, all survived the infection remaining clinically healthy during the 28 day observational period. Surviving animals presented protracted viremias with lower virus titers, when compared with those of animals inoculated with parental virus, and all of them developed a strong virus-specific antibody response. Importantly, all animals surviving ASFV-G-'AH108R infection were protected when challenged with the virulent parental strain ASFV-G. This report constitutes the first evidence that H108R gene is involved in ASFV virulence in swine and deletion of this gene may be used, if needed, as a tool to increase the attenuation of currently experimental vaccine to improve their safety profile.