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Title: Deletion of African swine fever virus Georgia 2007 virulence-associated gene 9GL (B119L) leads to virus attenuation in swine at low doses while inducing an effective protection against homologous challenge

Author
item O'DONNELL, VIVIAN - University Of Connecticut
item Holinka-Patterson, Lauren
item Krug, Peter
item GLADUE, DOUGLAS - University Of Connecticut
item CARLSON, JOLENE - Oak Ridge Institute For Science And Education (ORISE)
item Sanford, Brenton
item ALFANO, MARIALEXIA - Oak Ridge Institute For Science And Education (ORISE)
item KRAMER, EDWARD - Us Deparment Of Homeland Security
item LU, ZHIQIANG - Us Deparment Of Homeland Security
item Arzt, Jonathan
item REESE, BO - University Of Connecticut
item CARRILLO, CONSUELO - Animal And Plant Health Inspection Service (APHIS)
item RISATTI, GUILLERMO - University Of Connecticut
item Borca, Manuel

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/22/2015
Publication Date: 6/10/2015
Citation: O'Donnell, V., Holinka-Patterson, L.G., Krug, P.W., Gladue, D.P., Carlson, J., Sanford, B.J., Alfano, M., Kramer, E., Lu, Z., Arzt, J., Reese, B., Carrillo, C., Risatti, G., Borca, M.V. 2015. Deletion of African swine fever virus Georgia 2007 virulence-associated gene 9GL (B119L) leads to virus attenuation in swine at low doses while inducing an effective protection against homologous challenge. Journal of Virology. 89(16):8556-8566. DOI: 10.1128/JVI.00969-15.

Interpretive Summary: African swine fever virus (ASFV) causes a very contagious and often lethal viral disease of domestic pigs that has significant economic consequences for swine industry. Currently, there is no vaccine to control of African Swine Fever (ASF). Here, we demonstrated that, through genetic manipulation, we can attenuate a highly virulent strain currently causing an epidemic in the Caucasus region and Russia and threatening Eastern Europe. This attenuated strain is no longer lethal when inoculated in swine. This approach may be the basis for the development of attenuated vaccines against this devastating disease of swine.

Technical Abstract: African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for swine breeding. The control of African Swine Fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines have been derived from naturally occurring, cell culture-adapted, or genetically modified live attenuated ASFVs; however, these vaccines are only successful when protecting against homologous viruses. Recombinant viruses harboring engineered deletions of specific virulence-associated genes induce solid protection against the challenge with parental viruses. Deletion of the 9GL (B119L) gene in highly virulent ASFV Malawi Lil-20/1 (Mal) and Pretoriuskop/96/4 isolates (delta9GL viruses) produced an attenuated phenotype and protected swine against challenge with parental homologous isolates. Here we report the construction of a recombinant delta 9GL virus derived from the highly virulent ASFV Georgia 2007 (ASFV-G) isolate. As observed with delta9GL virus Malawi Lil-20/1, ASFV-G delta9GL has a decreased ability (relative to the parental virus) to replicate in primary swine macrophages in vitro. In vivo, ASFV-G delta9GL administered intramuscularly (IM) to swine at relatively high doses (10^4 HAD50) retains a virulent phenotype practically indistinguishable from the parental virus. Conversely, at low IM doses (10^2 HAD50), ASFV-G delta9GL does not induce disease. Therefore, deletion of the highly conserved 9GL (B119L) gene in the ASFV-G isolate does not completely reproduce the phenotypes observed with delta9GL viruses Malawi Lil-20/1 and Pretoriuskop/96/4, suggesting an isolate-specific effect on the induction of attenuation.