Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine
African swine fever virus (ASFV) is currently the most dreaded infectious disease affecting the global swine production industry. There is no commercial vaccine available, making the culling of infected animals the current solution to control outbreaks. Effective experimental vaccines have been deve...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/10/1185 |
| _version_ | 1797550458833731584 |
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| author | Douglas P. Gladue Vivian O’Donnell Elizabeth Ramirez-Medina Ayushi Rai Sarah Pruitt Elizabeth A. Vuono Ediane Silva Lauro Velazquez-Salinas Manuel V. Borca |
| author_facet | Douglas P. Gladue Vivian O’Donnell Elizabeth Ramirez-Medina Ayushi Rai Sarah Pruitt Elizabeth A. Vuono Ediane Silva Lauro Velazquez-Salinas Manuel V. Borca |
| author_sort | Douglas P. Gladue |
| collection | DOAJ |
| description | African swine fever virus (ASFV) is currently the most dreaded infectious disease affecting the global swine production industry. There is no commercial vaccine available, making the culling of infected animals the current solution to control outbreaks. Effective experimental vaccines have been developed by deleting virus genes associated with virulence. Deletion of the ASFV 9GL gene (∆9GL) has resulted in the attenuation of different ASFV strains, although the degree of attenuation varies across isolates. Here, we investigated the possibility of the increased safety of the experimental vaccine strain ASFV-G-Δ9GL by deleting two additional virus genes involved in pathogenesis, CD2v, a CD2 like viral encoded gene from the EP402R open reading frame (ORF), and C-type lectin-like viral gene, encoded from the EP153R ORF. Two new recombinant viruses were developed, ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, harboring two and three gene deletions, respectively. ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, but not ASFV-G-Δ9GL/ΔCD2v, had a decreased ability to replicate in vitro in swine macrophage cultures when compared with parental ASFV-G-Δ9GL. Importantly, ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R induced almost undetectable viremia levels when inoculated into domestic pigs and failed to protect them against challenge with parental virulent ASFV-Georgia, while ASFV-G-Δ9GL offered robust protection during challenge. Therefore, the deletion of CD2-like and C-type lectin-like genes significantly decreased the protective potential of ASFV-G-Δ9GL as a vaccine candidate. This study constitutes an example of the unpredictability of genetic manipulation involving the simultaneous deletion of multiple genes from the ASFV genome. |
| first_indexed | 2024-03-10T15:29:35Z |
| format | Article |
| id | doaj.art-730651df6603426297225d1908b8e4af |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T15:29:35Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-730651df6603426297225d1908b8e4af2023-11-20T17:46:01ZengMDPI AGViruses1999-49152020-10-011210118510.3390/v12101185Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental VaccineDouglas P. Gladue0Vivian O’Donnell1Elizabeth Ramirez-Medina2Ayushi Rai3Sarah Pruitt4Elizabeth A. Vuono5Ediane Silva6Lauro Velazquez-Salinas7Manuel V. Borca8Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAPlum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAPlum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAPlum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAPlum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAPlum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAPlum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAPlum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAPlum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USAAfrican swine fever virus (ASFV) is currently the most dreaded infectious disease affecting the global swine production industry. There is no commercial vaccine available, making the culling of infected animals the current solution to control outbreaks. Effective experimental vaccines have been developed by deleting virus genes associated with virulence. Deletion of the ASFV 9GL gene (∆9GL) has resulted in the attenuation of different ASFV strains, although the degree of attenuation varies across isolates. Here, we investigated the possibility of the increased safety of the experimental vaccine strain ASFV-G-Δ9GL by deleting two additional virus genes involved in pathogenesis, CD2v, a CD2 like viral encoded gene from the EP402R open reading frame (ORF), and C-type lectin-like viral gene, encoded from the EP153R ORF. Two new recombinant viruses were developed, ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, harboring two and three gene deletions, respectively. ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, but not ASFV-G-Δ9GL/ΔCD2v, had a decreased ability to replicate in vitro in swine macrophage cultures when compared with parental ASFV-G-Δ9GL. Importantly, ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R induced almost undetectable viremia levels when inoculated into domestic pigs and failed to protect them against challenge with parental virulent ASFV-Georgia, while ASFV-G-Δ9GL offered robust protection during challenge. Therefore, the deletion of CD2-like and C-type lectin-like genes significantly decreased the protective potential of ASFV-G-Δ9GL as a vaccine candidate. This study constitutes an example of the unpredictability of genetic manipulation involving the simultaneous deletion of multiple genes from the ASFV genome.https://www.mdpi.com/1999-4915/12/10/1185ASFVASFrecombinant virusesvaccineCD2EP402R |
| spellingShingle | Douglas P. Gladue Vivian O’Donnell Elizabeth Ramirez-Medina Ayushi Rai Sarah Pruitt Elizabeth A. Vuono Ediane Silva Lauro Velazquez-Salinas Manuel V. Borca Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine Viruses ASFV ASF recombinant viruses vaccine CD2 EP402R |
| title | Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine |
| title_full | Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine |
| title_fullStr | Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine |
| title_full_unstemmed | Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine |
| title_short | Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine |
| title_sort | deletion of cd2 like cd2v and c type lectin like ep153r genes from african swine fever virus georgia ∆9gl abrogates its effectiveness as an experimental vaccine |
| topic | ASFV ASF recombinant viruses vaccine CD2 EP402R |
| url | https://www.mdpi.com/1999-4915/12/10/1185 |
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