Location: Foreign Animal Disease ResearchTitle: X69R is a non-essential gene that when deleted from African swine fever does not affect virulence in swine
|RAMIREZ-MEDINA, ELIZABETH - University Of Connecticut|
|VUONO, ELIZABETH - University Of Mississippi|
|PRUITT, SARAH - Oak Ridge Institute For Science And Education (ORISE)|
|RAI, AYUSHI - Oak Ridge Institute For Science And Education (ORISE)|
|SILVA, EDIANE - University Of Kansas|
|VELAZQUEZ-SALINAS, LAURO - Oak Ridge Institute For Science And Education (ORISE)|
Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/17/2020
Publication Date: 8/21/2020
Citation: Ramirez-Medina, E., Vuono, E.A., Pruitt, S., Rai, A., Silva, E., Zhu, J.J., Velazquez-Salinas, L., Gladue, D.P., Borca, M.V. 2020. X69R is a non-essential gene that when deleted from African swine fever does not affect virulence in swine. Viruses. https://doi.org/10.3390/v12090918.
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 a delete a gene in ASFV, that that has never been deleted before and did not alter the pathogenesis of ASFV. We identified two cellular proteins that bind this gene giving insight into how ASFV interacts with cells.
Technical Abstract: African swine fever virus (ASFV) is currently causing devastating outbreaks in Asia and Europe and the ASFV strain Georgia (ASFV-G) is responsible for these outbreaks. ASFV-G is highly virulent and continues to be maintained in these outbreak areas apparently without suffering significant genomic or phenotypic changes. When comparing the genome of ASFV-G to other isolates, a so far uncharacterized gene, X69R, is highly conserved and, interestingly, is highly similar to another ASFV uncharacterized gene, J64R. All sequenced ASFV isolates have one or both of these genes, X69R and/or J64R, suggesting that the presence of at least one of these genes may be necessary for ASFV replication and or virulence. The X69R gene is present in the ASFV-G genome while J64R is absent. To assess the importance of X69R in ASFV-G functionality we developed a recombinant virus by deleting the X69R gene from the ASFV-G genome (ASFV-G-'X69R). ASFV-G-'X69R had the same replication kinetics in primary swine macrophage cultures as the parental ASFV-G, indicating that the X69R gene is not essential for ASFV-G viability or efficient replication in the main target cell during in vivo infection. In addition, swine intramuscularly inoculated with a low dose (10-2 HAD50) of ASFV-G-'X69R developed a clinical disease indistinguishable from that induced by the same dose of the virulent parental ASFV-G isolate. Viremia values of ASFV-G-'X69R did not significantly differ from those detected in animals infected with parental virus. Therefore, deletion of the X69R gene from ASFV-G does not affect virus replication or virulence in swine