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.
Highlights
African swine fever (ASF) is a contagious viral disease of swine
The amino acid sequences of both virus genes are highly conserved between the E70 and Georgia strains, we show here that while the UK deletion (ASFV-G ∆UK) from the ASF virus (ASFV)-G genome did not produce any decrease in virulence when compared with the parental virus, deletion of the NL gene produced partial attenuation of ASFV Georgia isolate (ASFV-G)
In vitro growth characteristics of ASFV-G-ΔNL and ASFV-G-ΔUK were evaluated in primary swine macrophage cell cultures, the primary cell targeted by ASFV during infection in swine, and
Summary
African swine fever (ASF) is a contagious viral disease of swine. The causative agent, ASF virus (ASFV), is a large enveloped virus containing a double-stranded (ds) DNA genome of approximately. Viruses 2019, 11, 599 spread to Eastern Europe, and South and East Asia, including China The virus causing this epidemic, ASFV Georgia 2007/1, is a highly virulent isolate that belongs to genotype II [3]. ASFVs containing genetically engineered deletions of specific virulence-associated genes are protected when challenged with homologous parental viruses. Animals immunized with these modified recombinant viruses were protected from disease when challenged with their homologous parental viruses These observations are the only experimental evidence supporting rational development of attenuated virus strains. The amino acid sequences of both virus genes are highly conserved between the E70 and Georgia strains, we show here that while the UK deletion (ASFV-G ∆UK) from the ASFV-G genome did not produce any decrease in virulence when compared with the parental virus, deletion of the NL gene produced partial attenuation of ASFV-G. We conclude that the differential effect of these two virus genes is dependent on other factors within the virus genome
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