The L83L ORF of African swine fever virus strain Georgia encodes for a non-essential gene that interacts with the host protein IL-1β

Borca, Manuel V.; O’Donnell, Vivian; Holinka, Lauren G.; Ramírez-Medina, Elizabeth; Clark, Benjamin A.; Vuono, Elizabeth; Berggren, Keith; Alfano, Marialexia; Carey, Lucas B.; Richt, Jüergen A.; Risatti, Guillermo R.; Gladue, Douglas P.

doi:10.1016/j.virusres.2018.03.017

Cited by 52 publications

(39 citation statements)

References 48 publications

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“…Two recombinant ASFVs were developed where the CD2v or the CD2v and EP153R genes were deleted: ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, respectively. Deletion of the CD2v or EP153R genes from the ASFV-G-Δ9GL genome was performed by substituting most or all the amino acid residues of those ORFs with the p72GFP cassette by homologous recombination following standard methodologies [ 17 ]. Genomic modification of ASFV-G-Δ9GL/ΔCD2v results in a partial deletion of the CD2v ORF while ASFV-G-Δ9GL/ΔCD2v/ΔEP153R harbors a deletion of the CD2v and EP153R ORFs ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

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

Gladue

O’Donnell

Ramírez-Medina

et al. 2020

Viruses

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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.

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Section: Resultsmentioning

confidence: 99%

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

Gladue

O’Donnell

Ramírez-Medina

et al. 2020

Viruses

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“…The functional characterization of virus genes has allowed the development of potential ASFV attenuated strains that have been used as experimental vaccine candidates [11,[28][29][30]. In that regard, a restricted number of virus genes have been successfully deleted in several recombinant viruses using an infectious ASFV backbone (e.g., genes as 9GL, lectin, UK, MGF, NL, CD2, Lectin) [11,15,[29][30][31][32][33][34][35][36][37], with a small number of genes determined to be essential for virus replication (e.g., EP152R, p30, p54, p72) [38][39][40]. This lack of information limits the current knowledge on most ASFV proteins to only ORF functional genomics and the predicted functions of these ORFs.…”

Section: Discussionmentioning

confidence: 99%

“…Although it has been postulated that the virus modulates the host immune response to facilitate the progress of infection (reviewed by Reis et al 2016 [37]), the precise molecular mechanisms involved allowing ASFV to manipulate host cellular processes for its own survival are still not well understood. Very few host proteins are known to directly interact with ASFV proteins [33,[40][41][42], and further work is required to determine possible virus-host interactions that may be involved in determining the pathogenesis of ASFV in swine. In this study we identified that the viral protein MGF360-16R specifically binds to host proteins, genes SERTAD3 and SDCBP, regulatory factors of cell transcription.…”

Section: Discussionmentioning

confidence: 99%

The MGF360-16R ORF of African Swine Fever Virus Strain Georgia Encodes for a Nonessential Gene That Interacts with Host Proteins SERTAD3 and SDCBP

Ramírez-Medina

Vuono

Velazquez‐Salinas

et al. 2020

Viruses

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African swine fever virus (ASFV) causes a contagious and frequently lethal disease of pigs with significant economic consequences to the swine industry. The ASFV genome encodes for more than 160 genes, but only a few of them have been studied in detail. Here we report the characterization of open reading frame (ORF) MGF360-16R. Kinetic studies of virus RNA transcription demonstrated that the MGF360-16R gene is transcribed as a late virus protein. Analysis of host–protein interactions for the MGF360-16R gene using a yeast two-hybrid screen identified SERTA domain containing 3 (SERTAD3) and syndecan-binding protein (SDCBP) as host protein binding partners. SERTAD3 and SDCBP are both involved in nuclear transcription and SDCBP has been shown to be involved in virus traffic inside the host cell. Interaction between MGF360-16R and SERTAD3 and SDCBP host proteins was confirmed in eukaryotic cells transfected with plasmids expressing MGF360-16R and SERTAD3 or SDCBP fused to fluorescent tags. A recombinant ASFV lacking the MGF360-16R gene (ASFV-G-ΔMGF360-16R) was developed from the highly virulent field isolate Georgia2007 (ASFV-G) and was used to show that MGF360-16R is a nonessential gene. ASFV-G-ΔMGF360-16R had a similar replication ability in primary swine macrophage cell cultures when compared to its parental virus ASFV-G. Experimental infection of domestic pigs showed that ASFV-G-ΔMGF360-16R is as virulent as the parental virus ASFV-G.

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“…Comparative growth curves were done as previously described 26,27 . between ASFV-G-Δ8DR and parental ASFV-G were performed in primary swine macrophage cell cultures.…”

Section: Methodsmentioning

confidence: 99%

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

Borca

O’Donnell

Holinka

et al. 2020

Sci Rep

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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-Δ8DR) does not significantly alter the virulence of the virus. ASFV-G-Δ8DR inoculated intramuscularly or intranasally (in a range of 10 2 to 10 4 tciD 50) 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-Δ8DR 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. African swine fever virus (ASFV) a large double stranded DNA virus and etiological agent that causes African swine fever (ASF). Depending on the isolate, swine infected with ASFV can have disease that ranges from sub-clinical to disease in which can be highly lethal 1. ASF has been endemic in several sub-Saharan African countries and also in Sardinia (Italy). Recently, outbreaks of ASF have occurred in Eastern Europe and southeast Asia. These outbreaks have all originated with from an outbreak in the Caucasus region that occurred in 2007 2. The isolate that is involved in the current outbreak called Georgia/2007 is highly contagious and lethal in domestic pigs. This high rate of lethality has the potential to cause large losses of domestic pigs 3. There are no vaccines currently available to prevent ASF (1). Development of experimental live-attenuated ASF vaccines, have mainly relied on the production of recombinant field isolates by genetic manipulation, in which one or more genes have been deleted from the field isolate 4-6. Therefore, understanding the role of viral genes in virulence and their possible manipulation to develop attenuated virus strains to produce experimental vaccines is a critical issue. Since its original description, the CD2-like African swine fever virus (ASFV) gene (8DR) has been the focus of intense research. 8DR protein has been shown to be responsible for mediating hemadsorption 7,8 , being critical in virus replication in tick cells 9 , immunomodulate the host response 10 , and is actively involved in the induction of protective immune response 11,12 .

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The L83L ORF of African swine fever virus strain Georgia encodes for a non-essential gene that interacts with the host protein IL-1β

Cited by 52 publications

References 48 publications

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

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

The MGF360-16R ORF of African Swine Fever Virus Strain Georgia Encodes for a Nonessential Gene That Interacts with Host Proteins SERTAD3 and SDCBP

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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