The differential effect of the deletion of African swine fever virus virulence-associated genes in the induction of attenuation of the highly virulent Georgia strain

Authors: RAMIREZ-MEDINA, ELIZABETH - Oak Ridge Institute For Science And Education (ORISE); VUONO, ELIZABETH - Mississippi State University; O'DONNELL, VIVIAN - Animal And Plant Health Inspection Service (APHIS); HOLINKA, LAUREN - The Jackson Laboratory; SILVA, EDIANE - Kansas State University; RAI, AYUSHI - Oak Ridge Institute For Science And Education (ORISE); PRUITT, SARAH - Oak Ridge Institute For Science And Education (ORISE); CARRILLO, CONSUELO - Animal And Plant Health Inspection Service (APHIS); Gladue, Douglas; Borca, Manuel

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/27/2019
Publication Date: 7/2/2019
Citation: Ramirez-Medina, E., Vuono, E., O'Donnell, V., Holinka, L.G., Silva, E., Rai, A., Pruitt, S., Carrillo, C., Gladue, D.P., Borca, M.V. 2019. The differential effect of the deletion of African swine fever virus virulence-associated genes in the induction of attenuation of the highly virulent Georgia strain. Virology. https://doi.org/10.3390/v11070599.
DOI: https://doi.org/10.3390/v11070599

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 add an additional gene deletion to our current vaccine platform. Addition of this additional gene deletion causes our current experimental live attenuated vaccine to have a decreased ability of the vaccine to grow when given to swine. This results in poor immunity, thus our attempts to increase the number of genes deleted in our vaccine platform were unsuccessful.

Technical Abstract: African swine fever virus (ASFV) is the etiological agent of an often lethal disease of domestic pigs, African swine fever (ASF). The ASFV Georgia 2007 isolate (ASFV-G) is responsible for the current epidemic situation in Europe and Asia. Genetically modified ASFVs containing deletions of virulence-associated genes have produced attenuated phenotypes and induced protective immunity in swine. Here we describe the differential behavior of two viral genes, NL (DP71L) and UK (DP96R), both originally described as being involved in virus virulence. Deletion of either of these genes efficiently attenuated ASFV strain E70. We demonstrated that deletion of the UK gene from the ASFV-G genome did not decrease virulence when compared to the parental virus. Conversely, deletion of the NL gene produced a heterogeneous response, with early death in one of the animals and transient fever in the other animals. With this knowledge, we attempted to increase the safety profile of the previously reported experimental vaccine ASFV-G'9GL/'UK by deleting the NL gene. A triple gene deletion virus was produced, ASFV-G'9GL/'NL/'UK. Although ASFV-G'9GL/'NL/'UK replicated in primary cell cultures of swine macrophages, it demonstrated a severe replication deficiency in pigs, failing to induce protection against challenge with parental ASFV-G.