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Differential Effect of the Deletion of African Swine Fever Virus Virulence-Associated Genes in the Induction of Attenuation of the Highly Virulent Georgia Strain

1
Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
2
Animal and Plant Health Inspection, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA
*
Authors to whom correspondence should be addressed.
Current affiliation: The Jackson Laboratory, Ten Discovery Drive, Farmington, CT 06032, USA.
Viruses 2019, 11(7), 599; https://doi.org/10.3390/v11070599
Received: 31 May 2019 / Revised: 25 June 2019 / Accepted: 27 June 2019 / Published: 2 July 2019
(This article belongs to the Special Issue Porcine Viruses 2019)
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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-GΔ9GL/ΔUK by deleting the NL gene. A triple gene-deletion virus was produced, ASFV-GΔ9GL/ΔNL/ΔUK. Although ASFV-GΔ9GL/ΔNL/ΔUK 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. View Full-Text
Keywords: ASFV; ASF; African swine fever; porcine ASFV; ASF; African swine fever; porcine
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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. Differential Effect of the Deletion of African Swine Fever Virus Virulence-Associated Genes in the Induction of Attenuation of the Highly Virulent Georgia Strain. Viruses 2019, 11, 599.

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