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Research Project: COUNTERMEASURES TO CONTROL FOREIGN ANIMAL DISEASES OF SWINE

Location: Foreign Animal Disease Research

Title: African swine fever virus Georgia isolate harboring deletions of MGF360 and MGF505 genes is attenuated in swine and confers protection against challenge with the virulent parental virus

Author
item O'DONNELL, VIVIAN - University Of Connecticut
item Holinka-Patterson, Lauren
item GLADUE, DOUGLAS - University Of Connecticut
item Sanford, Brenton
item Krug, Peter
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: 3/19/2015
Publication Date: 6/1/2015
Publication URL: http://handle.nal.usda.gov/10113/61569
Citation: O'Donnell, V., Holinka-Patterson, L.G., Gladue, D.P., Sanford, B.J., Krug, P.W., Lu, Z., Arzt, J., Reese, B., Carrillo, C., Risatti, G.R., Borca, M.V. 2015. African swine fever virus Georgia isolate harboring deletions of MGF360 and MGF505 genes is attenuated in swine and confers protection against challenge with the virulent parental virus. Journal of Virology. 89(11):6048-6056.

Interpretive Summary: African swine fever (ASF) is a devastating viral disease that causes high mortality in pigs. The main problem for controlling ASF is the lack of effective vaccines. The disease is originally from Africa, but there have been outbreaks in the Caribbean and in Europe resulting in the death of millions of pigs. The ASF virus (ASFV) is very resistant and can be transmitted to animals fed with contaminated pork products. Since 2007 ASF outbreaks have been reported in the Caucasus region, and the ASFV has spread into Russia. More recently, ASF has been detected in wild pigs in Poland. ARS' researchers describe the development of an attenuated ASFV derived from the highly pathogenic ASFV currently circulating the Caucasus (ASFV-G). The attenuated strain was obtained by removing six genes from the pathogenic ASF-G strain. The resulting virus, when inoculated in pigs, did not cause any disease. Furthermore, 28 days later they were exposed to a lethal dose of ASF-G strain, the pigs survived. This is the first report of an experimental vaccine candidate that induces a solid protection against the highly virulent ASFV-G. Further studies will be necessary to develop this into an effective vaccine against this devastating disease.

Technical Abstract: African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The control of African Swine Fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines have been developed using genetically modified-live attenuated ASFVs where viral genes involved in virus virulence were removed from the genome. Multigene families (MGF) 360 and 505 represent a group of genes sharing partial sequence and structural identities that have been connected with ASFV host range specificity, blocking of the host innate response, and virus virulence. Here we report the construction of a recombinant virus (ASFV-G-DeltaMGF) derived from the highly virulent ASFV Georgia 2007 isolate (ASFV-G) by specifically deleting six genes belonging to MGF360/MGF505: MGF505-1R, MGF360-12L, MGF360-13L, MGF-14L, MGF505-2R and MGF505-3R. ASFV-G-DeltaMGF replicates as efficiently in primary swine macrophage cell cultures as the parental virus. In vivo, ASFV-G-DeltaMGF is completely attenuated in swine, since pigs inoculated intramuscularly with either 102 or 104 HAD50 remained healthy without signs of the disease. Importantly, when these animals were subsequently exposed to highly virulent parental ASFV-G, no signs of the disease were observed. This is the first report demonstrating the role of MGF genes acting as independent determinants of ASFV virulence. Additionally, ASFV-G-DeltaMGF is the first experimental vaccine reported to induce protection when challenged with the highly virulent and epidemiologically relevant ASFV-G.