Dataset Information

Deletion of CD2-like gene from the genome of African swine fever virus strain Georgia does not attenuate virulence in swine.

ABSTRACT: The CD2-like African swine fever virus (ASFV) gene 8DR, (also known as EP402R) encodes for a structural transmembrane glycoprotein that has been shown to mediate hemadsorption and be involved in host immunomodulation as well as the induction of protective immune response. In addition, several natural ASFV isolates showing decreased virulence in swine has been shown to be non-hemadsorbing suggesting an association between altered or deleted forms of 8DR and virus attenuation. Here we demonstrate that deletion of 8DR gene from the genome of ASFV Georgia2010 isolate (ASFV-G-?8DR) does not significantly alter the virulence of the virus. ASFV-G-?8DR inoculated intramuscularly or intranasally (in a range of 102 to 104 TCID50) produced a clinical disease in domestic pigs indistinguishable from that induced by the same doses of the virulent parental ASFV Georgia2010 isolate. In addition, viremia values in ASFV-G-?8DR do not differ from those detected in animals infected with parental virus. Therefore, deletion of 8DR gene is not associated with a noticeable decrease in virulence of the ASFV Georgia isolate.

SUBMITTER: Borca MV

PROVIDER: S-EPMC6965178 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Deletion of CD2-like gene from the genome of African swine fever virus strain Georgia does not attenuate virulence in swine.

Borca Manuel V MV O'Donnell Vivian V Holinka Lauren G LG Risatti Guillermo R GR Ramirez-Medina Elizabeth E Vuono Elizabeth A EA Shi Jishu J Pruitt Sarah S Rai Ayushi A Silva Ediane E Velazquez-Salinas Lauro L Gladue Douglas P DP

Scientific reports 20200116 1

The CD2-like African swine fever virus (ASFV) gene 8DR, (also known as EP402R) encodes for a structural transmembrane glycoprotein that has been shown to mediate hemadsorption and be involved in host immunomodulation as well as the induction of protective immune response. In addition, several natural ASFV isolates showing decreased virulence in swine has been shown to be non-hemadsorbing suggesting an association between altered or deleted forms of 8DR and virus attenuation. Here we demonstrate ...[more]

PMID: 31949276

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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 CD2-like gene from the genome of African swine fever virus strain Georgia does not attenuate virulence in swine.

Publications

Deletion of CD2-like gene from the genome of African swine fever virus strain Georgia does not attenuate virulence in swine.

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