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African Swine Fever Virus 2021
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African Swine Fever Virus 2021

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 73471

Special Issue Editor

Dr. Manuel Borca

E-Mail Website
Guest Editor
USDA ARS Plum Island Animal Disease Center, Greenport, NY, USA
Interests: all aspects of ASFV research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the last few years, African swine fever (ASF) has become one of the most feared infectious diseases affecting swine production and the commercialization of swine derived products in vast geographical areas of the world. The etiological agent, ASF virus (ASFV), is a large, structurally complex virus with a double stranded DNA genome encoding for over 150 proteins. Although the disease was originally identified in the 1920s, research on ASF has dramatically intensified in just the last ten years. This Special Issue of Viruses will be devoted to covering different aspects of ASFV research. Special emphasis will be placed on reports focused on molecular mechanisms mediating virus virulence, virus pathogenesis in domestic and wild swine, host immune response involved in protection against infection, development of different types of experimental vaccines, molecular basis of virus replication, virus structure, and novel/improved diagnostic methodologies. Contributions will be accepted in the format of original research reports, reviews covering very specific aspects of ASF research, and opinion articles. This Special Issue of Viruses expects to offer scientists working in ASF a forum to share high quality research in a variety of thematic areas of ASF research.

Dr. Manuel Borca
Guest Editor

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Keywords

  • ASF
  • ASFV
  • virus virulence
  • pathogenesis in natural hosts
  • protective host immune response
  • vaccine development
  • virus replication
  • virus structure/morphogenesis
  • ASF diagnostic

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Published Papers (19 papers)

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14 pages, 3618 KiB  
Article
Bayesian Phylodynamic Analysis Reveals the Dispersal Patterns of African Swine Fever Virus
by Zhao-Ji Shen, Hong Jia, Chun-Di Xie, Jurmt Shagainar, Zheng Feng, Xiaodong Zhang, Kui Li and Rong Zhou
Viruses 2022, 14(5), 889; https://doi.org/10.3390/v14050889 - 25 Apr 2022
Cited by 6 | Viewed by 2726
Abstract
The evolutionary and demographic history of African swine fever virus (ASFV) is potentially quite valuable for developing efficient and sustainable management strategies. In this study, we performed phylogenetic, phylodynamic, and phylogeographic analyses of worldwide ASFV based on complete ASFV genomes, B646L gene, and [...] Read more.
The evolutionary and demographic history of African swine fever virus (ASFV) is potentially quite valuable for developing efficient and sustainable management strategies. In this study, we performed phylogenetic, phylodynamic, and phylogeographic analyses of worldwide ASFV based on complete ASFV genomes, B646L gene, and E183L gene sequences obtained from NCBI to understand the epidemiology of ASFV. Bayesian phylodynamic analysis and phylogenetic analysis showed highly similar results of group clustering between E183L and the complete genome. The evidence of migration and the demographic history of ASFV were also revealed by the Bayesian phylodynamic analysis. The evolutionary rate was estimated to be 1.14 × 10−5 substitution/site/year. The large out-migration from the viral population in South Africa played a crucial role in spreading the virus worldwide. Our study not only provides resources for the better utilization of genomic data but also reveals the comprehensive worldwide evolutionary history of ASFV with a broad sampling window across ~70 years. The characteristics of the virus spatiotemporal transmission are also elucidated, which could be of great importance for devising strategies to control the virus. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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16 pages, 3922 KiB  
Article
Effects of the NF-κB Signaling Pathway Inhibitor BAY11-7082 in the Replication of ASFV
by Qi Gao, Yunlong Yang, Yongzhi Feng, Weipeng Quan, Yizhuo Luo, Heng Wang, Jiachen Zheng, Xiongnan Chen, Zhao Huang, Xiaojun Chen, Runda Xu, Guihong Zhang and Lang Gong
Viruses 2022, 14(2), 297; https://doi.org/10.3390/v14020297 - 31 Jan 2022
Cited by 13 | Viewed by 3494
Abstract
African swine fever virus (ASFV) mainly infects the monocyte/macrophage lineage of pigs and regulates the production of cytokines that influence host immune responses. Several studies have reported changes in cytokine production after infection with ASFV, but the regulatory mechanisms have not yet been [...] Read more.
African swine fever virus (ASFV) mainly infects the monocyte/macrophage lineage of pigs and regulates the production of cytokines that influence host immune responses. Several studies have reported changes in cytokine production after infection with ASFV, but the regulatory mechanisms have not yet been elucidated. Therefore, the aim of this study was to examine the immune response mechanism of ASFV using transcriptomic and proteomic analyses. Through multi-omics joint analysis, it was found that ASFV infection regulates the expression of the host NF-B signal pathway and related cytokines. Additionally, changes in the NF-κB signaling pathway and IL-1β and IL-8 expression in porcine alveolar macrophages (PAMs) infected with ASFV were examined. Results show that ASFV infection activates the NF-κB signaling pathway and up-regulates the expression of IL-1β and IL-8. The NF-κB inhibitor BAY11-7082 inhibited the expression profiles of phospho-NF-κB p65, p-IκB, and MyD88 proteins, and inhibited ASFV-induced NF-κB signaling pathway activation. Additionally, the results show that the NF-κB inhibitor BAY11-7082 can inhibit the replication of ASFV and can inhibit IL-1β and, IL-8 expression. Overall, the findings of this study indicate that ASFV infection activates the NF-κB signaling pathway and up-regulates the expression of IL-1β and IL-8, and inhibits the replication of ASFV by inhibiting the NF-κB signaling pathway and interleukin-1 beta and interleukin-8 production. These findings not only provide new insights into the molecular mechanism of the association between the NF-κB signaling pathway and ASFV infection, but also indicate that the NF-κB signaling pathway is a potential immunomodulatory pathway that controls ASF. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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13 pages, 1846 KiB  
Article
Performance Characteristics of Real-Time PCRs for African Swine Fever Virus Genome Detection—Comparison of Twelve Kits to an OIE-Recommended Method
by Jutta Pikalo, Tessa Carrau, Paul Deutschmann, Melina Fischer, Kore Schlottau, Martin Beer and Sandra Blome
Viruses 2022, 14(2), 220; https://doi.org/10.3390/v14020220 - 24 Jan 2022
Cited by 6 | Viewed by 3298
Abstract
African swine fever (ASF) is a major threat to pig production, and real-time PCR (qPCR) protocols are an integral part of ASF laboratory diagnosis. With the pandemic spread of ASF, commercial kits have risen on the market. In Germany, the kits have to [...] Read more.
African swine fever (ASF) is a major threat to pig production, and real-time PCR (qPCR) protocols are an integral part of ASF laboratory diagnosis. With the pandemic spread of ASF, commercial kits have risen on the market. In Germany, the kits have to go through an approval process and thus, general validation can be assumed. However, they have never been compared to each other. In this study, 12 commercial PCR kits were compared to an OIE-recommended method. Samples representing different matrices, genome loads, and genotypes were included in a panel that was tested under diagnostic conditions. The comparison included user-friendliness, internal controls, and the time required. All qPCRs were able to detect ASFV genome in different matrices across all genotypes and disease courses. With one exception, there were no significant differences when comparing the overall mean. The overall specificity was 100% (95% CI 87.66–100), and the sensitivity was between 95% and 100% (95% CI 91.11–100). As can be expected, variability concerned samples with low genome load. To conclude, all tests were fit for purpose. The test system can therefore be chosen based on compatibility and prioritization of the internal control system. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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11 pages, 1573 KiB  
Article
I267L Is Neither the Virulence- Nor the Replication-Related Gene of African Swine Fever Virus and Its Deletant Is an Ideal Fluorescent-Tagged Virulence Strain
by Yanyan Zhang, Junnan Ke, Jingyuan Zhang, Huixian Yue, Teng Chen, Qian Li, Xintao Zhou, Yu Qi, Rongnian Zhu, Shuchao Wang, Faming Miao, Shoufeng Zhang, Nan Li, Lijuan Mi, Jinjin Yang, Jinmei Yang, Xun Han, Lidong Wang, Ying Li and Rongliang Hu
Viruses 2022, 14(1), 53; https://doi.org/10.3390/v14010053 - 29 Dec 2021
Cited by 10 | Viewed by 1909
Abstract
African swine fever virus (ASFV) is the causative agent of African swine fever (ASF) which reaches up to 100% case fatality in domestic pigs and wild boar and causes significant economic losses in the swine industry. Lack of knowledge of the function of [...] Read more.
African swine fever virus (ASFV) is the causative agent of African swine fever (ASF) which reaches up to 100% case fatality in domestic pigs and wild boar and causes significant economic losses in the swine industry. Lack of knowledge of the function of ASFV genes is a serious impediment to the development of the safe and effective vaccine. Herein, I267L was identified as a relative conserved gene and an early expressed gene. A recombinant virus (SY18ΔI267L) with I267L gene deletion was produced by replacing I267L of the virulent ASFV SY18 with enhanced green fluorescent protein (EGFP) cassette. The replication kinetics of SY18ΔI267L is similar to that of the parental isolate in vitro. Moreover, the doses of 102.0 TCID50 (n = 5) and 105.0 TCID50 (n = 5) SY18ΔI267L caused virulent phenotype, severe clinical signs, viremia, high viral load, and mortality in domestic pigs inoculated intramuscularly as the virulent parental virus strain. Therefore, the deletion of I267L does not affect the replication or the virulence of ASFV. Utilizing the fluorescent-tagged virulence deletant can be easy to gain a visual result in related research such as the inactivation effect of some drugs, disinfectants, extracts, etc. on ASFV. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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14 pages, 2031 KiB  
Article
Evaluation of Cellular Immunity with ASFV Infection by Swine Leukocyte Antigen (SLA)—Peptide Tetramers
by Wenqiang Sun, He Zhang, Wenhui Fan, Lihong He, Teng Chen, Xintao Zhou, Yu Qi, Lei Sun, Rongliang Hu, Tingrong Luo, Wenjun Liu and Jing Li
Viruses 2021, 13(11), 2264; https://doi.org/10.3390/v13112264 - 12 Nov 2021
Cited by 7 | Viewed by 2914
Abstract
African swine fever virus (ASFV) causes acute hemorrhagic fever in domestic pigs and wild boars, resulting in incalculable economic losses to the pig industry. As the mechanism of viral infection is not clear, protective antigens have not been discovered or identified. In this [...] Read more.
African swine fever virus (ASFV) causes acute hemorrhagic fever in domestic pigs and wild boars, resulting in incalculable economic losses to the pig industry. As the mechanism of viral infection is not clear, protective antigens have not been discovered or identified. In this study, we determined that the p30, pp62, p72, and CD2v proteins were all involved in the T cell immune response of live pigs infected with ASFV, among which p72 and pp62 proteins were the strongest. Panoramic scanning was performed on T cell epitopes of the p72 protein, and three high-frequency positive epitopes were selected to construct a swine leukocyte antigen (SLA)-tetramer, and ASFV-specific T cells were detected. Subsequently, the specific T cell and humoral immune responses of ASFV-infected pigs and surviving pigs were compared. The results demonstrate that the specific T cellular immunity responses gradually increased during the infection and were higher than that in the surviving pigs in the late stages of infection. The same trend was observed in specific humoral immune responses, which were highest in surviving pigs. In general, our study provides key information for the exploration of ASFV-specific immune responses and the development of an ASFV vaccine. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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16 pages, 3273 KiB  
Article
Comparison of the Proteomes of Porcine Macrophages and a Stable Porcine Cell Line after Infection with African Swine Fever Virus
by Elisabeth Wöhnke, Walter Fuchs, Luise Hartmann, Ulrike Blohm, Sandra Blome, Thomas C. Mettenleiter and Axel Karger
Viruses 2021, 13(11), 2198; https://doi.org/10.3390/v13112198 - 01 Nov 2021
Cited by 14 | Viewed by 3325
Abstract
African swine fever virus (ASFV), causing an OIE-notifiable viral disease of swine, is spreading over the Eurasian continent and threatening the global pig industry. Here, we conducted the first proteome analysis of ASFV-infected primary porcine monocyte-derived macrophages (moMΦ). In parallel to moMΦ isolated [...] Read more.
African swine fever virus (ASFV), causing an OIE-notifiable viral disease of swine, is spreading over the Eurasian continent and threatening the global pig industry. Here, we conducted the first proteome analysis of ASFV-infected primary porcine monocyte-derived macrophages (moMΦ). In parallel to moMΦ isolated from different pigs, the stable porcine cell line WSL-R was infected with a recombinant of ASFV genotype IX strain “Kenya1033”. The outcome of the infections was compared via quantitative mass spectrometry (MS)-based proteome analysis. Major differences with respect to the expression of viral proteins or the host cell response were not observed. However, cell-specific expression of some individual viral proteins did occur. The observed modulations of the host proteome were mainly related to cell characteristics and function. Overall, we conclude that both infection models are suitable for use in the study of ASFV infection in vitro. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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11 pages, 2198 KiB  
Article
The Efficacy of Disinfection on Modified Vaccinia Ankara and African Swine Fever Virus in Various Forest Soil Types
by Franziska Tanneberger, Ahmed Abd El Wahed, Melina Fischer, Sandra Blome and Uwe Truyen
Viruses 2021, 13(11), 2173; https://doi.org/10.3390/v13112173 - 28 Oct 2021
Cited by 5 | Viewed by 2131
Abstract
African swine fever (ASF) has become a global threat to the pig industry and wild suids. Within Europe, including Germany, affected wild boar populations play a major role. Fencing and carcass removal in combination with the reduction in environmental contamination are key to [...] Read more.
African swine fever (ASF) has become a global threat to the pig industry and wild suids. Within Europe, including Germany, affected wild boar populations play a major role. Fencing and carcass removal in combination with the reduction in environmental contamination are key to control further spread. The handling of the ASF virus (ASFV) is restricted to high-containment conditions in Germany. According to the regulation of the German Veterinarian Society (DVG), modified vaccinia Ankara virus (MVAV) is the virus of choice to determine the efficacy of disinfection for enveloped viruses. The aim of this study was to use the MVAV as a guide to select the best possible disinfectant solution and concentration for the inactivation of ASFV in soil. Both viruses were tested simultaneously. In this study, two layers (top and mineral soil) of soil types from six different locations in Saxony, Germany, were collected. The tenacity of ASFV and MVAV were tested at various time points (0.5 to 72 h). The capabilities of different concentrations of peracetic acid and citric acid (approx. 0.1 to 2%) to inactivate the viruses in the selected soil types with spiked high protein load were examined under appropriate containment conditions. Around 2–3 Log10 (TCID50) levels of reduction in the infectivity of both ASFV and MVAV were observed in all soil types starting after two hours. For MVAV, a 4 Log10 loss was recorded after 72 h. A total of 0.1% of peracetic acid (5 L/m2) was sufficient to inactivate the viruses. A 4 log10 reduction in the infectivity of MVAV was noticed by applying 1% citric acid, while a 2 log10 decline was recorded with ASFV. In conclusion, comparing MVAV to ASFV for efficacy screening of disinfectant solutions has revealed many similarities. Peracetic acid reduced the infectivity of both viruses independently of the soil type and the existence of a high organic soiling. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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14 pages, 1779 KiB  
Article
Meat Exudate for Detection of African Swine Fever Virus Genomic Material and Anti-ASFV Antibodies
by Chukwunonso Onyilagha, Mikyla Nash, Orlando Perez, Melissa Goolia, Alfonso Clavijo, Juergen A. Richt and Aruna Ambagala
Viruses 2021, 13(9), 1744; https://doi.org/10.3390/v13091744 - 01 Sep 2021
Cited by 7 | Viewed by 3204
Abstract
African swine fever (ASF) is one of the most important viral diseases of pigs caused by the ASF virus (ASFV). The virus is highly stable over a wide range of temperatures and pH and can survive in meat and meat products for several [...] Read more.
African swine fever (ASF) is one of the most important viral diseases of pigs caused by the ASF virus (ASFV). The virus is highly stable over a wide range of temperatures and pH and can survive in meat and meat products for several months, leading to long-distance transmission of ASF. Whole blood, serum, and organs from infected pigs are used routinely as approved sample types in the laboratory diagnosis of ASF. However, these sample types may not always be available. Here, we investigated meat exudate as an alternative sample type for the detection of ASFV-specific nucleic acids and antibodies. Pigs were infected with various ASFV strains: the highly virulent ASFV Malawi LIL 18/2 strain, the moderately-virulent ASFV Estonia 2014 strain, or the low-virulent ASFV OURT/88/3 strain. The animals were euthanized on different days post-infection (dpi), and meat exudates were collected and tested for the presence of ASFV-specific nucleic acids and antibodies. Animals infected with the ASFV Malawi LIL 18/2 developed severe clinical signs and succumbed to the infection within seven dpi, while pigs infected with ASFV Estonia 2014 also developed clinical signs but survived longer, with a few animals seroconverting before succumbing to the ASFV infection or being euthanized as they reached humane endpoints. Pigs infected with ASFV OURT/88/3 developed transient fever and seroconverted without mortality. ASFV genomic material was detected in meat exudate from pigs infected with ASFV Malawi LIL 18/2 and ASFV Estonia 2014 at the onset of viremia but at a lower amount when compared to the corresponding whole blood samples. Low levels of ASFV genomic material were detected in the whole blood of ASFV OURT/88/3-infected pigs, and no ASFV genomic material was detected in the meat exudate of these animals. Anti-ASFV antibodies were detected in the serum and meat exudate derived from ASFV OURT/88/3-infected pigs and in some of the samples derived from the ASFV Estonia 2014-infected pigs. These results indicate that ASFV genomic material and anti-ASFV antibodies can be detected in meat exudate, indicating that this sample can be used as an alternative sample type for ASF surveillance when routine sample types are unavailable or are not easily accessible. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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12 pages, 1473 KiB  
Article
Rapid Extraction and Detection of African Swine Fever Virus DNA Based on Isothermal Recombinase Polymerase Amplification Assay
by Arianna Ceruti, Rea Maja Kobialka, Judah Ssekitoleko, Julius Boniface Okuni, Sandra Blome, Ahmed Abd El Wahed and Uwe Truyen
Viruses 2021, 13(9), 1731; https://doi.org/10.3390/v13091731 - 31 Aug 2021
Cited by 17 | Viewed by 3283
Abstract
African swine fever virus (ASFV) is the causative agent of a deadly disease in pigs and is spread rapidly across borders. Samples collected from suspected cases must be sent to the reference laboratory for diagnosis using polymerase chain reaction (PCR). In this study, [...] Read more.
African swine fever virus (ASFV) is the causative agent of a deadly disease in pigs and is spread rapidly across borders. Samples collected from suspected cases must be sent to the reference laboratory for diagnosis using polymerase chain reaction (PCR). In this study, we aimed to develop a simple DNA isolation step and real-time recombinase polymerase amplification (RPA) assay for rapid detection of ASFV. RPA assay based on the p72 encoding B646L gene of ASFV was established. The assays limit of detection and cross-reactivity were investigated. Diagnostic performance was examined using 73 blood and serum samples. Two extraction approaches were tested: silica-column-based extraction method and simple non-purification DNA isolation (lysis buffer and heating, 70 °C for 20 min). All results were compared with well-established real-time PCR. In a field deployment during a disease outbreak event in Uganda, 20 whole blood samples were tested. The assay’s analytical sensitivity was 3.5 DNA copies of molecular standard per µL as determined by probit analysis on eight independent assay runs. The ASFV RPA assay only detected ASFV genotypes. Compared to real-time PCR, RPA diagnostic sensitivity and specificity were 100%. Using the heating/lysis buffer extraction procedure, ASFV-RPA revealed better tolerance to inhibitors than real-time PCR (97% and 38% positivity rate, respectively). In Uganda, infected animals were identified before the appearance of fever. The ASFV-RPA assay is shown to be as sensitive and specific as real-time PCR. Moreover, the combination of the simple extraction protocol allows its use at the point of need to improve control measures. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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27 pages, 9236 KiB  
Article
African Swine Fever Virus CD2v Protein Induces β-Interferon Expression and Apoptosis in Swine Peripheral Blood Mononuclear Cells
by Sabal Chaulagain, Gustavo A. Delhon, Sushil Khatiwada and Daniel L. Rock
Viruses 2021, 13(8), 1480; https://doi.org/10.3390/v13081480 - 28 Jul 2021
Cited by 28 | Viewed by 4562
Abstract
African swine fever (ASF) is a hemorrhagic disease of swine characterized by massive lymphocyte depletion in lymphoid tissues due to the apoptosis of B and T cells, a process likely triggered by factors released or secreted by infected macrophages. ASFV CD2v (EP402R) has [...] Read more.
African swine fever (ASF) is a hemorrhagic disease of swine characterized by massive lymphocyte depletion in lymphoid tissues due to the apoptosis of B and T cells, a process likely triggered by factors released or secreted by infected macrophages. ASFV CD2v (EP402R) has been implicated in viral virulence and immunomodulation in vitro; however, its actual function(s) remains unknown. We found that CD2v expression in swine PK15 cells induces NF-κB-dependent IFN-β and ISGs transcription and an antiviral state. Similar results were observed for CD2v protein treated swine PBMCs and macrophages, the major ASFV target cell. Notably, treatment of swine PBMCs and macrophages with CD2v protein induced apoptosis. Immunoprecipitation and colocalization studies revealed that CD2v interacts with CD58, the natural host CD2 ligand. Additionally, CD58 knockdown in cells or treatment of cells with an NF-κB inhibitor significantly reduced CD2v-mediated NF-κB activation and IFN-β induction. Further, antibodies directed against CD2v inhibited CD2v-induced NF-κB activation and IFN-β transcription in cells. Overall, results indicate that ASFV CD2v activates NF-κB, which induces IFN signaling and apoptosis in swine lymphocytes/macrophages. We propose that CD2v released from infected macrophages may be a significant factor in lymphocyte apoptosis observed in lymphoid tissue during ASFV infection in pigs. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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10 pages, 13317 KiB  
Article
Growth Kinetics and Protective Efficacy of Attenuated ASFV Strain Congo with Deletion of the EP402 Gene
by Galina Koltsova, Andrey Koltsov, Sergey Krutko, Natalia Kholod, Edan R. Tulman and Denis Kolbasov
Viruses 2021, 13(7), 1259; https://doi.org/10.3390/v13071259 - 28 Jun 2021
Cited by 15 | Viewed by 2994
Abstract
African swine fever (ASF) is an emerging disease threat to the swine industry worldwide. There is no vaccine against ASF, and progress is hindered by a lack of knowledge concerning the extent of ASFV strain diversity and the viral antigens conferring type-specific protective [...] Read more.
African swine fever (ASF) is an emerging disease threat to the swine industry worldwide. There is no vaccine against ASF, and progress is hindered by a lack of knowledge concerning the extent of ASFV strain diversity and the viral antigens conferring type-specific protective immunity in pigs. We have previously demonstrated that homologous ASFV serotype-specific proteins CD2v (EP402R) and/or C-type lectin are required for protection against challenge with the virulent ASFV strain Congo (Genotype I, Serogroup 2), and we have identified T-cell epitopes on CD2v which may be associated with serotype-specific protection. Here, using a cell-culture adapted derivative of the ASFV strain Congo (Congo-a) with specific deletion of the EP402R gene (ΔCongoCD2v) in swine vaccination/challenge experiments, we demonstrated that deletion of the EP402R gene results in the failure of ΔCongoCD2v to induce protection against challenge with the virulent strain Congo (Congo-v). While ΔCongoCD2v growth kinetics in COS-1 cells and primary swine macrophage culture were almost identical to parental Congo-a, replication of ΔCongoCD2v in vivo was significantly reduced compared with parental Congo-a. Our data support the idea that the CD2v protein is important for the ability of homologous live-attenuated vaccines to induce protective immunity against the ASFV strain Congo challenge in vivo. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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14 pages, 2422 KiB  
Article
African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation
by Lucía Barrado-Gil, Ana del Puerto, Inmaculada Galindo, Miguel Ángel Cuesta-Geijo, Isabel García-Dorival, Carlos Maluquer de Motes and Covadonga Alonso
Viruses 2021, 13(6), 1160; https://doi.org/10.3390/v13061160 - 17 Jun 2021
Cited by 23 | Viewed by 3234
Abstract
African swine fever virus (ASFV) is an acute and persistent swine virus with a high economic burden that encodes multiple genes to evade host immune response. In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded [...] Read more.
African swine fever virus (ASFV) is an acute and persistent swine virus with a high economic burden that encodes multiple genes to evade host immune response. In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune and inflammatory signaling. Transient overexpression of UBCv1 impaired activation of NF-κB and AP-1 transcription factors induced by several agonists of these pathways. In contrast, activation of IRF3 and ISRE signaling upon stimulation with TRIFΔRIP, cGAS/STING or RIG-I-CARD remained unaltered. Experiments aimed at mapping UBCv1 inhibitory activity indicated that this viral protein acts upstream or at the level step of IKKβ. In agreement with this, UBCv1 was able to block p65 nuclear translocation upon cytokine stimulation, a key event in NF-ĸB signaling. Additionally, A549 stably transduced for UBCv1 showed a significant decrease in the levels of NF-ĸB dependent genes. Interestingly, despite the well-defined capacity of UBCv1 to conjugate ubiquitin chains, a mutant disabled for ubiquitylation activity retained similar immunomodulatory activity as the wild-type enzyme, suggesting that the two functions are segregated. Altogether these data suggest that ASFV UBCv1 manipulates the innate immune response targeting the NF-κB and AP-1 pathways and opens new questions about the multifunctionality of this enzyme. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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20 pages, 4192 KiB  
Article
Combined Short and Long-Read Sequencing Reveals a Complex Transcriptomic Architecture of African Swine Fever Virus
by Gábor Torma, Dóra Tombácz, Zsolt Csabai, Norbert Moldován, István Mészáros, Zoltán Zádori and Zsolt Boldogkői
Viruses 2021, 13(4), 579; https://doi.org/10.3390/v13040579 - 30 Mar 2021
Cited by 10 | Viewed by 3676
Abstract
African swine fever virus (ASFV) is a large DNA virus belonging to the Asfarviridae family. Despite its agricultural importance, little is known about the fundamental molecular mechanisms of this pathogen. Short-read sequencing (SRS) can produce a huge amount of high-precision sequencing reads for [...] Read more.
African swine fever virus (ASFV) is a large DNA virus belonging to the Asfarviridae family. Despite its agricultural importance, little is known about the fundamental molecular mechanisms of this pathogen. Short-read sequencing (SRS) can produce a huge amount of high-precision sequencing reads for transcriptomic profiling, but it is inefficient for comprehensively annotating transcriptomes. Long-read sequencing (LRS) can overcome some of SRS’s limitations, but it also has drawbacks, such as low-coverage and high error rate. The limitations of the two approaches can be surmounted by the combined use of these techniques. In this study, we used Illumina SRS and Oxford Nanopore Technologies LRS platforms with multiple library preparation methods (amplified and direct cDNA sequencings and native RNA sequencing) for constructing the ASFV transcriptomic atlas. This work identified many novel transcripts and transcript isoforms and annotated the precise termini of previously described RNAs. This study identified a novel species of ASFV transcripts, the replication origin-associated RNAs. Additionally, we discovered several nested genes embedded into larger canonical genes. In contrast to the current view that the ASFV transcripts are monocistronic, we detected a significant extent of polycistronism, although a large proportion of these transcripts are expressed in low abundance. A multifaceted meshwork of transcriptional overlaps was also discovered. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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14 pages, 3830 KiB  
Article
African Swine Fever Virus Structural Protein p17 Inhibits Cell Proliferation through ER Stress—ROS Mediated Cell Cycle Arrest
by Nengwen Xia, Hui Wang, Xueliang Liu, Qi Shao, Da Ao, Yulin Xu, Sen Jiang, Jia Luo, Jiajia Zhang, Nanhua Chen, François Meurens, Wanglong Zheng and Jianzhong Zhu
Viruses 2021, 13(1), 21; https://doi.org/10.3390/v13010021 - 24 Dec 2020
Cited by 23 | Viewed by 3905
Abstract
African swine fever virus (ASFV) is a highly pathogenic large DNA virus that causes African swine fever (ASF) in domestic pigs and wild boars. The p17 protein, encoded by the D117L gene, is a major transmembrane protein of the capsid and the inner [...] Read more.
African swine fever virus (ASFV) is a highly pathogenic large DNA virus that causes African swine fever (ASF) in domestic pigs and wild boars. The p17 protein, encoded by the D117L gene, is a major transmembrane protein of the capsid and the inner lipid envelope. The aim of this study was to investigate the effects of p17 on cell proliferation and the underlying mechanisms of action. The effects of p17 on cell proliferation, cell cycle, apoptosis, oxidative stress, and endoplasmic reticulum (ER) stress have been examined in 293T, PK15, and PAM cells, respectively. The results showed that p17 reduced cell proliferation by causing cell cycle arrest at G2/M phase. Further, p17-induced oxidative stress and increased the level of intracellular reactive oxygen species (ROS). Decreasing the level of ROS partially reversed the cell cycle arrest and prevented the decrease of cell proliferation induced by p17 protein. In addition, p17-induced ER stress, and alleviating ER stress decreased the production of ROS and prevented the decrease of cell proliferation induced by p17. Taken together, this study suggests that p17 can inhibit cell proliferation through ER stress and ROS-mediated cell cycle arrest, which might implicate the involvement of p17 in ASF pathogenesis. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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11 pages, 1413 KiB  
Article
Live Attenuated African Swine Fever Viruses as Ideal Tools to Dissect the Mechanisms Involved in Cross-Protection
by Elisabeth Lopez, Juanita van Heerden, Laia Bosch-Camós, Francesc Accensi, Maria Jesus Navas, Paula López-Monteagudo, Jordi Argilaguet, Carmina Gallardo, Sonia Pina-Pedrero, Maria Luisa Salas, Jeremy Salt and Fernando Rodriguez
Viruses 2020, 12(12), 1474; https://doi.org/10.3390/v12121474 - 21 Dec 2020
Cited by 28 | Viewed by 3388
Abstract
African swine fever (ASF) has become the major threat for the global swine industry. Furthermore, the epidemiological situation of African swine fever virus (ASFV) in some endemic regions of Sub-Saharan Africa is worse than ever, with multiple virus strains and genotypes currently circulating [...] Read more.
African swine fever (ASF) has become the major threat for the global swine industry. Furthermore, the epidemiological situation of African swine fever virus (ASFV) in some endemic regions of Sub-Saharan Africa is worse than ever, with multiple virus strains and genotypes currently circulating in a given area. Despite the recent advances on ASF vaccine development, there are no commercial vaccines yet, and most of the promising vaccine prototypes available today have been specifically designed to fight the genotype II strains currently circulating in Europe, Asia, and Oceania. Previous results from our laboratory have demonstrated the ability of BA71∆CD2, a recombinant LAV lacking CD2v, to confer protection against homologous (BA71) and heterologous genotype I (E75) and genotype II (Georgia2007/01) ASFV strains, both belonging to same clade (clade C). Here, we extend these results using BA71∆CD2 as a tool trying to understand ASFV cross-protection, using phylogenetically distant ASFV strains. We first observed that five out of six (83.3%) of the pigs immunized once with 106 PFU of BA71∆CD2 survived the tick-bite challenge using Ornithodoros sp. soft ticks naturally infected with RSA/11/2017 strain (genotype XIX, clade D). Second, only two out of six (33.3%) survived the challenge with Ken06.Bus (genotype IX, clade A), which is phylogenetically more distant to BA71∆CD2 than the RSA/11/2017 strain. On the other hand, homologous prime-boosting with BA71∆CD2 only improved the survival rate to 50% after Ken06.Bus challenge, all suffering mild ASF-compatible clinical signs, while 100% of the pigs immunized with BA71∆CD2 and boosted with the parental BA71 virulent strain survived the lethal challenge with Ken06.Bus, without almost no clinical signs of the disease. Our results confirm that cross-protection is a multifactorial phenomenon that not only depends on sequence similarity. We believe that understanding this complex phenomenon will be useful for designing future vaccines for ASF-endemic areas. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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Review

Jump to: Research, Other

30 pages, 1825 KiB  
Review
African Swine Fever in Wild Boar in Europe—A Review
by Carola Sauter-Louis, Franz J. Conraths, Carolina Probst, Ulrike Blohm, Katja Schulz, Julia Sehl, Melina Fischer, Jan Hendrik Forth, Laura Zani, Klaus Depner, Thomas C. Mettenleiter, Martin Beer and Sandra Blome
Viruses 2021, 13(9), 1717; https://doi.org/10.3390/v13091717 - 30 Aug 2021
Cited by 76 | Viewed by 9015
Abstract
The introduction of genotype II African swine fever (ASF) virus, presumably from Africa into Georgia in 2007, and its continuous spread through Europe and Asia as a panzootic disease of suids, continues to have a huge socio-economic impact. ASF is characterized by hemorrhagic [...] Read more.
The introduction of genotype II African swine fever (ASF) virus, presumably from Africa into Georgia in 2007, and its continuous spread through Europe and Asia as a panzootic disease of suids, continues to have a huge socio-economic impact. ASF is characterized by hemorrhagic fever leading to a high case/fatality ratio in pigs. In Europe, wild boar are especially affected. This review summarizes the currently available knowledge on ASF in wild boar in Europe. The current ASF panzootic is characterized by self-sustaining cycles of infection in the wild boar population. Spill-over and spill-back events occur from wild boar to domestic pigs and vice versa. The social structure of wild boar populations and the spatial behavior of the animals, a variety of ASF virus (ASFV) transmission mechanisms and persistence in the environment complicate the modeling of the disease. Control measures focus on the detection and removal of wild boar carcasses, in which ASFV can remain infectious for months. Further measures include the reduction in wild boar density and the limitation of wild boar movements through fences. Using these measures, the Czech Republic and Belgium succeeded in eliminating ASF in their territories, while the disease spread in others. So far, no vaccine is available to protect wild boar or domestic pigs reliably against ASF. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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20 pages, 1444 KiB  
Review
African Swine Fever Virus as a Difficult Opponent in the Fight for a Vaccine—Current Data
by Hanna Turlewicz-Podbielska, Anna Kuriga, Rafał Niemyjski, Grzegorz Tarasiuk and Małgorzata Pomorska-Mól
Viruses 2021, 13(7), 1212; https://doi.org/10.3390/v13071212 - 23 Jun 2021
Cited by 22 | Viewed by 5206
Abstract
Prevention and control of African swine fever virus (ASFV) in Europe, Asia, and Africa seem to be extremely difficult in view of the ease with which it spreads, its high resistance to environmental conditions, and the many obstacles related to the introduction of [...] Read more.
Prevention and control of African swine fever virus (ASFV) in Europe, Asia, and Africa seem to be extremely difficult in view of the ease with which it spreads, its high resistance to environmental conditions, and the many obstacles related to the introduction of effective specific immunoprophylaxis. Biological properties of ASFV indicate that the African swine fever (ASF) pandemic will continue to develop and that only the implementation of an effective and safe vaccine will ensure a reduction in the spread of ASFV. At present, vaccines against ASF are not available. The latest approaches to the ASFV vaccine’s design concentrate on the development of either modified live vaccines by targeted gene deletion from different isolates or subunit vaccines. The construction of an effective vaccine is hindered by the complex structure of the virus, the lack of an effective continuous cell line for the isolation and propagation of ASFV, unpredictable and stain-specific phenotypes after the genetic modification of ASFV, a risk of reversion to virulence, and our current inability to differentiate infected animals from vaccinated ones. Moreover, the design of vaccines intended for wild boars and oral administration is desirable. Despite several obstacles, the design of a safe and effective vaccine against ASFV seems to be achievable. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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Other

Jump to: Research, Review

12 pages, 1570 KiB  
Brief Report
Deletion of the K145R and DP148R Genes from the Virulent ASFV Georgia 2007/1 Isolate Delays the Onset, but Does Not Reduce Severity, of Clinical Signs in Infected Pigs
by Anusyah Rathakrishnan, Ana L. Reis, Lynnette C. Goatley, Katy Moffat and Linda K. Dixon
Viruses 2021, 13(8), 1473; https://doi.org/10.3390/v13081473 - 28 Jul 2021
Cited by 8 | Viewed by 2466
Abstract
African swine fever virus causes a frequently fatal disease of domestic pigs and wild boar that has a high economic impact across 3 continents. The large double-stranded DNA genome codes for approximately 160 proteins. Many of these have unknown functions and this hinders [...] Read more.
African swine fever virus causes a frequently fatal disease of domestic pigs and wild boar that has a high economic impact across 3 continents. The large double-stranded DNA genome codes for approximately 160 proteins. Many of these have unknown functions and this hinders our understanding of the virus and host interactions. The purpose of the study was to evaluate the role of two virus proteins, K145R and DP148R, in virus replication in macrophages and virulence in pigs. To do this, the DP148R gene, alone or in combination with the K145R gene, was deleted from the virulent genotype II Georgia 2007/1 isolate. Neither of these deletions reduced the ability of the viruses to replicate in porcine macrophages compared to the parental wild-type virus. Pigs infected with GeorgiaΔDP148R developed clinical and post-mortem signs and high viremia, typical of acute African swine fever, and were culled on day 6 post-infection. The additional deletion of the K145R gene delayed the onset of clinical signs and viremia in pigs by 3 days, but pigs showed signs of acute African swine fever and were culled on days 10 or 13 post-infection. The results show that the deletion of DP148R did not attenuate the genotype II Georgia 2007/1 isolate, contrary to the results obtained with the genotype I Benin97/1 isolate. Additional deletion of the K145R gene delayed clinical signs, but infected pigs reached the humane endpoint. The deletion of additional genes would be required to attenuate the virus. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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14 pages, 243 KiB  
Opinion
Thoughts on African Swine Fever Vaccines
by Daniel L. Rock
Viruses 2021, 13(5), 943; https://doi.org/10.3390/v13050943 - 20 May 2021
Cited by 29 | Viewed by 5181
Abstract
African swine fever (ASF) is an acute viral hemorrhagic disease of domestic swine with mortality rates approaching 100%. Devastating ASF outbreaks and continuing epidemics starting in the Caucasus region and now in the Russian Federation, Europe, China, and other parts of Southeast Asia [...] Read more.
African swine fever (ASF) is an acute viral hemorrhagic disease of domestic swine with mortality rates approaching 100%. Devastating ASF outbreaks and continuing epidemics starting in the Caucasus region and now in the Russian Federation, Europe, China, and other parts of Southeast Asia (2007 to date) highlight its significance. ASF strain Georgia-07 and its derivatives are now endemic in extensive regions of Europe and Asia and are “out of Africa” forever, a situation that poses a grave if not an existential threat to the swine industry worldwide. While our current concern is Georgia-07, other emerging ASFV strains will threaten for the indefinite future. Economic analysis indicates that an ASF outbreak in the U.S. would result in approximately $15 billion USD in losses, assuming the disease is rapidly controlled and the U.S. is able to reenter export markets within two years. ASF’s potential to spread and become endemic in new regions, its rapid and efficient transmission among pigs, and the relative stability of the causative agent ASF virus (ASFV) in the environment all provide significant challenges for disease control. Effective and robust methods, including vaccines for ASF response and recovery, are needed immediately. Full article
(This article belongs to the Special Issue African Swine Fever Virus 2021)
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