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Deletion of African Swine Fever Virus Histone-like Protein, A104R from the Georgia Isolate Drastically Reduces Virus Virulence in Domestic Pigs.

ABSTRACT: African swine fever virus (ASFV) is the etiological agent of a frequently lethal disease, ASF, affecting domestic and wild swine. Currently, ASF is causing a pandemic affecting pig production in Eurasia. There are no vaccines available, and therefore control of the disease is based on culling infected animals. We report here that deletion of the ASFV gene A104R, a virus histone-like protein, from the genome of the highly virulent ASFV-Georgia2010 (ASFV-G) strain induces a clear decrease in virus virulence when experimentally inoculated in domestic swine. A recombinant virus lacking the A104R gene, ASFV-G-∆A104R, was developed to assess the role of the A104R gene in disease production in swine. Domestic pigs were intramuscularly inoculated with 10² HAD₅₀ of ASFV-G-∆A104R, and compared with animals that received a similar dose of virulent ASFV-G. While all ASFV-G inoculated animals developed a fatal form of the disease, animals receiving ASFV-G-∆A104R survived the challenge, remaining healthy during the 28-day observational period, with the exception of only one showing a protracted but fatal form of the disease. ASFV-G-∆A104R surviving animals presented protracted viremias with reduced virus titers when compared with those found in animals inoculated with ASFV-G, and all of them developed a strong virus-specific antibody response. This is the first report demonstrating that the A104R gene is involved in ASFV virulence in domestic swine, suggesting that A104R deletion may be used to increase the safety profile of currently experimental vaccines.

SUBMITTER: Ramirez-Medina E

PROVIDER: S-EPMC9146580 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Deletion of African Swine Fever Virus Histone-like Protein, A104R from the Georgia Isolate Drastically Reduces Virus Virulence in Domestic Pigs.

Ramirez-Medina Elizabeth E Vuono Elizabeth A EA Pruitt Sarah S Rai Ayushi A Espinoza Nallely N Valladares Alyssa A Silva Ediane E Velazquez-Salinas Lauro L Borca Manuel V MV Gladue Douglas P DP

Viruses 20220522 5

African swine fever virus (ASFV) is the etiological agent of a frequently lethal disease, ASF, affecting domestic and wild swine. Currently, ASF is causing a pandemic affecting pig production in Eurasia. There are no vaccines available, and therefore control of the disease is based on culling infected animals. We report here that deletion of the ASFV gene A104R, a virus histone-like protein, from the genome of the highly virulent ASFV-Georgia2010 (ASFV-G) strain induces a clear decrease in virus ...[more]

PMID: 35632853

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Project description:African swine fever (ASF) is a severe hemorrhagic infectious disease in pigs caused by African swine fever virus (ASFV), leading to devastating economic losses in epidemic regions. Its control currently depends on thorough culling and clearance of the diseased and surrounding suspected pigs. An ASF vaccine has been extensively explored for years worldwide, especially in hog-intensive areas where it is highly desired, but it is still unavailable for numerous reasons. Here, we report another ASF vaccine candidate, named SY18ΔI226R, bearing a deletion of the I226R gene with a replacement of an enhanced green fluorescent protein (eGFP) expression cassette at the right end of the viral genome. This deletion results in the complete loss of virulence of SY18 as the gene-deleted strain does not cause any clinical symptoms in all pigs inoculated with a dosage of either 104.0 or 107.0 50% tissue culture infective doses (TCID50). Apparent viremia with a gradual decline was monitored, while virus shedding was detected only occasionally in oral or anal swabs. ASFV-specific antibody appeared at 9 days postinoculation. After intramuscular challenge with its parental strain ASFV SY18 at 21 days postinoculation, all the challenged pigs survived, without obvious febrile or abnormal clinical signs. No viral DNA could be detected upon the dissection of any tissue when viremia disappeared. These results indicated that SY18ΔI226R is safe in swine and elicits robust immunity to virulent ASFV infection. IMPORTANCE Outbreaks of African swine fever have resulted in devastating losses to the swine industry worldwide, but there is currently no commercial vaccine available. Although several vaccine candidates have been reported, none has been approved for use for several reasons, especially ones concerning biosafety. Here, we identified a new undescribed functional gene, I226R. When deleted from the ASFV genome, the virus completely loses its virulence in swine. Importantly, pigs infected with this gene-deleted virus were resistant to infection by intramuscular challenge with 102.5 or 104.0 TCID50 of its virulent parental virus. Furthermore, the nucleic acid of the gene-deleted virus and its virulent parental virus was rarely detected from oral or anal swabs. Viruses could not be detected in any tissues after necropsy when viremia became negative, indicating that robust immunity was achieved. Therefore, SY18ΔI226R is a novel, ideal, and efficacious vaccine candidate for genotype II ASF.

Dataset Information

Deletion of African Swine Fever Virus Histone-like Protein, A104R from the Georgia Isolate Drastically Reduces Virus Virulence in Domestic Pigs.

Publications

Deletion of African Swine Fever Virus Histone-like Protein, A104R from the Georgia Isolate Drastically Reduces Virus Virulence in Domestic Pigs.

Similar Datasets

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