Pathogenesis of African swine fever virus inOrnithodorosticks

AbstractAfrican swine fever virus (ASFV) is the only known DNA arbovirus and the sole member of the family Asfarviridae. It causes a lethal, hemorrhagic disease in domestic pigs. ASFV is enzootic in sub-Saharan Africa and is maintained in a sylvatic cycle by infecting both wild members of the Suidae (e.g. warthogs) and the argasid tickOrnithodoros porcinus porcinus. The pathogenesis of ASFV inO. porcinus porcinusticks is characterized by a low infectious dose, lifelong infection, efficient transmission to both pigs and ticks, and low mortality until after the first oviposition. ASFV pathogenesis in warthogs is characterized by an inapparent infection with transient, low viremic titers. ThusO. porcinus porcinusticks probably constitute the most important natural vector of ASFV, although both the mammalian and tick hosts are probably required for the maintenance of ASFV in the sylvatic cycle. The mechanism of ASFV transmission from the sylvatic cycle to domestic pigs is probably through infected ticks feeding on pigs. In addition toO. porcinus porcinus, a number of North American, Central American and Caribbean species ofOrnithodoroshave been shown to be potential vectors of ASFV.

Download Full-text

Persistent domestic circulation of African swine fever virus in Tanzania, 2015–2017

BMC Veterinary Research ◽

10.1186/s12917-020-02588-w ◽

2020 ◽

Vol 16 (1) ◽

Author(s):

Clara M. Yona ◽

Merijn Vanhee ◽

Edgar Simulundu ◽

Mariam Makange ◽

Hans J. Nauwynck ◽

...

Keyword(s):

Phylogenetic Analysis ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Composite Likelihood ◽

Control Measures ◽

Disease Spread ◽

Hemorrhagic Disease ◽

Sylvatic Cycle ◽

East African Community ◽

Domestic Pigs

Abstract Background African swine fever (ASF) is a highly fatal viral hemorrhagic disease of domestic pigs that threatens livelihoods and food security. In Africa, ASF virus (ASFV) circulates in sylvatic (transmission between warthogs and soft argasid ticks) and domestic (transmission between domestic pigs) cycles, with outbreaks resulting from ASFV spill-over from sylvatic cycle. A number of outbreaks were reported in different parts of Tanzania between 2015 and 2017. The present study investigated ASFV transmission patterns through viral DNA sequencing and phylogenetic analysis. A total of 3120 tissue samples were collected from 2396 domestic pigs during outbreaks at different locations in Tanzania between 2015 and 2017. Partial sequencing of the B646L (p72) gene was conducted for diagnostic confirmation and molecular characterization of ASFV. Phylogenetic analysis to study the relatedness of current ASFV with those that caused previous outbreaks in Tanzania and representatives of all known 24 ASFV was performed using the Maximum Composite Likelihood model with 1000 bootstrap replications in MEGA 6.0. Results ASFV was confirmed to cause disease in sampled domestic pigs. ASFV genotypes II, IX, and X were detected from reported outbreaks in 2015–2017. The current ASFV isolates were similar to those recently documented in the previous studies in Tanzania. The similarities of these isolates suggests for continuous circulation of ASFV with virus maintenance within the domestic pigs. Conclusions Genetic analysis confirmed the circulation of ASFV genotypes II, IX, and X by partial B646L (p72) gene sequencing. The similarities of current isolates to previously isolated Tanzanian isolates and pattern of disease spread suggest for continuous circulation of ASF with virus’ maintenance in the domestic pigs. Although certain viral genotypes seem to be geographically restricted into certain zones within Tanzania, genotype II seems to expand its geographical range northwards with the likelihood of spreading to other states of the East African Community. The spread of ASFV is due to breach of quarantine and transportation of infected pigs via major highways. Appropriate control measures including zoosanitary measures and quarantine enforcement are recommended to prevent ASF domestic circulation in Tanzania.

Download Full-text

Persistent domestic circulation of African swine fever virus in Tanzania, 2015-2017

10.21203/rs.2.15337/v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Clara M. Yona ◽

Merijn Vanhee ◽

Edgar Simulundu ◽

Mariam Makange ◽

Hans Nauwynck ◽

...

Keyword(s):

Phylogenetic Analysis ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Composite Likelihood ◽

Control Measures ◽

Disease Spread ◽

Hemorrhagic Disease ◽

Sylvatic Cycle ◽

East African Community ◽

Domestic Pigs

Abstract Background African swine fever (ASF) is a highly fatal viral hemorrhagic disease of domestic pigs that threatens livelihoods and food security. In Africa, ASF virus (ASFV) circulates in sylvatic (transmission between warthogs and soft argasid ticks) and domestic (transmission between domestic pigs) cycles, with outbreaks resulting from ASFV spill-over from sylvatic cycle. A number of outbreaks were reported in different parts of Tanzania between 2015 and 2017. The present study investigated ASFV transmission patterns through virus genotyping and phylogenetic analysis. Results ASFV was confirmed to cause outbreaks in sampled domestic pigs. ASFV genotypes II, IX, and X were detected from reported outbreaks in 2015-2017. The current ASFV isolates were similar to those recently documented in the previous studies in Tanzania. The similarities of these isolates suggests for continuous circulation of ASFV with virus maintenance within the domestic pigs. Methods A total of 3120 tissue samples were collected from 2396 domestic pigs during outbreaks at different locations in Tanzania between 2015 and 2017. Partial sequencing of the B646L (p72) gene was conducted for diagnostic confirmation and molecular characterization of ASFV. Phylogenetic analysis to study the relatedness of current ASFV with those that caused previous outbreaks in Tanzania and representatives of all known 24 ASFV was performed using the Maximum Composite Likelihood model with 1000 bootstrap replications in MEGA 6.0. Conclusions Genetic analysis confirmed the circulation of ASFV genotypes II, IX, and X by partial B646L (p72) gene sequencing. The similarities of current isolates to previously isolated Tanzanian isolates and pattern of disease spread suggest for continuous circulation of ASF with virus’ maintenance in the domestic pigs. Although certain viral genotypes seem to be geographically restricted into certain zones within Tanzania, genotype II seems to expand its geographical range northwards with the likelihood of spreading to other states of the East African Community. The spread of ASFV is due to breach of quarantine and transportation of affected pigs via major highways. Appropriate control measures including zoosanitary measures and quarantine measures adherence are recommended to prevent ASF domestic circulation in Tanzania.

Download Full-text

Cytokine Storm in Domestic Pigs Induced by Infection of Virulent African Swine Fever Virus

Frontiers in Veterinary Science ◽

10.3389/fvets.2020.601641 ◽

2021 ◽

Vol 7 ◽

Author(s):

Shuchao Wang ◽

Jingyuan Zhang ◽

Yanyan Zhang ◽

Jinjin Yang ◽

Lidong Wang ◽

...

Keyword(s):

Inflammatory Cytokines ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Post Inoculation ◽

Hemorrhagic Disease ◽

Cytokine Storm ◽

Domestic Pigs ◽

Tnf Α ◽

Anti Inflammatory

African swine fever, caused by African swine fever virus (ASFV), is a highly contagious hemorrhagic disease of domestic pigs. The current continent-wide pandemic has persisted for over 10 years, and its economy-devastating effect was highlighted after spreading to China, which possesses half of the world pig industry. So far, development of an effective and safe vaccine has not been finished largely due to the knowledge gaps in pathogenesis and immunology, particularly the role of cytokines in the host's immune response. Therefore, we performed experiments in domestic pigs to analyze the kinetics of representative circulating interferons (IFNs), interleukins (ILs), growth factors, tumor necrosis factors (TNFs), and chemokines induced by infection of type II virulent ASFV SY18. Pigs infected with this Chinese prototypical isolate developed severe clinical manifestations mostly from 3 days post inoculation (dpi) and died from 7 to 8 dpi. Serum analysis revealed a trend of robust and sustained elevation of pro-inflammatory cytokines including TNF-α, IFN-α, IL-1β, IL-6, IL-8, IL-12, IL-18, RANTES (regulated upon activation, normal T cell expressed and secreted), and IFN-γ-induced protein 10 (IP-10) from 3 dpi, but not the anti-inflammatory cytokines IL-10 and transforming growth factor-β (TGF-β). Moreover, secondary drastic increase of the levels of TNF-α, IL-1β, IL-6, and IL-8, as well as elevated IL-10, was observed at the terminal phase of infection. This pattern of cytokine secretion clearly drew an image of a typical cytokine storm characterized by delayed and dysregulated initiation of the secretion of pro-inflammatory cytokine and imbalanced pro- and anti-inflammatory response, which paved a way for further understanding of the molecular basis of ASFV pathogenesis.

Download Full-text

Persistent domestic circulation of African swine fever virus in Tanzania, 2015-2017

10.21203/rs.2.15337/v3 ◽

2020 ◽

Author(s):

Clara M. Yona ◽

Merijn Vanhee ◽

Edgar Simulundu ◽

Mariam Makange ◽

Hans Nauwynck ◽

...

Keyword(s):

African Swine Fever Virus ◽

African Swine Fever ◽

Composite Likelihood ◽

Control Measures ◽

Disease Spread ◽

Hemorrhagic Disease ◽

Sylvatic Cycle ◽

Tissue Samples ◽

East African Community ◽

Domestic Pigs

Abstract BackgroundAfrican swine fever (ASF) is a highly fatal viral hemorrhagic disease of domestic pigs that threatens livelihoods and food security. In Africa, ASF virus (ASFV) circulates in sylvatic (transmission between warthogs and soft argasid ticks) and domestic (transmission between domestic pigs) cycles, with outbreaks resulting from ASFV spill-over from sylvatic cycle. A number of outbreaks were reported in different parts of Tanzania between 2015 and 2017. The present study investigated ASFV transmission patterns through viral DNA sequencing and phylogenetic analysis.ResultsASFV was confirmed to cause disease in sampled domestic pigs. ASFV genotypes II, IX, and X were detected from reported outbreaks in 2015-2017. The current ASFV isolates were similar to those recently documented in the previous studies in Tanzania. The similarities of these isolates suggests for continuous circulation of ASFV with virus maintenance within the domestic pigs.MethodsA total of 3120 tissue samples were collected from 2396 domestic pigs during outbreaks at different locations in Tanzania between 2015 and 2017. Partial sequencing of the B646L (p72) gene was conducted for diagnostic confirmation and molecular characterization of ASFV. Phylogenetic analysis to study the relatedness of current ASFV with those that caused previous outbreaks in Tanzania and representatives of all known 24 ASFV was performed using the Maximum Composite Likelihood model with 1000 bootstrap replications in MEGA 6.0.ConclusionsGenetic analysis confirmed the circulation of ASFV genotypes II, IX, and X by partial B646L (p72) gene sequencing. The similarities of current isolates to previously isolated Tanzanian isolates and pattern of disease spread suggest for continuous circulation of ASF with virus’ maintenance in the domestic pigs. Although certain viral genotypes seem to be geographically restricted into certain zones within Tanzania, genotype II seems to expand its geographical range northwards with the likelihood of spreading to other states of the East African Community. The spread of ASFV is due to breach of quarantine and transportation of infected pigs via major highways. Appropriate control measures including zoosanitary measures and quarantine enforcement are recommended to prevent ASF domestic circulation in Tanzania.

Download Full-text

Persistent domestic circulation of African swine fever virus in Tanzania, 2010-2017

10.21203/rs.2.15337/v1 ◽

2019 ◽

Author(s):

Clara M. Yona ◽

Merijn Vanhee ◽

Edgar Simulundu ◽

Mariam Makange ◽

Hans Nauwynck ◽

...

Keyword(s):

African Swine Fever Virus ◽

African Swine Fever ◽

Control Measures ◽

Nucleotide Sequencing ◽

Hemorrhagic Disease ◽

East African ◽

Sylvatic Cycle ◽

Tissue Samples ◽

East African Community ◽

Domestic Pigs

Download Full-text

African swine fever: how can global spread be prevented?

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2009.0098 ◽

2009 ◽

Vol 364 (1530) ◽

pp. 2683-2696 ◽

Cited By ~ 204

Author(s):

Solenne Costard ◽

Barbara Wieland ◽

William de Glanville ◽

Ferran Jori ◽

Rebecca Rowlands ◽

...

Keyword(s):

African Swine Fever Virus ◽

African Swine Fever ◽

Sub Saharan Africa ◽

Economic Losses ◽

Sylvatic Cycle ◽

Global Spread ◽

The Indian Ocean ◽

Sub Saharan ◽

Global Movements ◽

Global Threat

African swine fever (ASF) is a devastating haemorrhagic fever of pigs with mortality rates approaching 100 per cent. It causes major economic losses, threatens food security and limits pig production in affected countries. ASF is caused by a large DNA virus, African swine fever virus (ASFV). There is no vaccine against ASFV and this limits the options for disease control. ASF has been confined mainly to sub-Saharan Africa, where it is maintained in a sylvatic cycle and/or among domestic pigs. Wildlife hosts include wild suids and arthropod vectors. The relatively small numbers of incursions to other continents have proven to be very difficult to eradicate. Thus, ASF remained endemic in the Iberian peninsula until the mid-1990s following its introductions in 1957 and 1960 and the disease has remained endemic in Sardinia since its introduction in 1982. ASF has continued to spread within Africa to previously uninfected countries, including recently the Indian Ocean islands of Madagascar and Mauritius. Given the continued occurrence of ASF in sub-Saharan Africa and increasing global movements of people and products, it is not surprising that further transcontinental transmission has occurred. The introduction of ASF to Georgia in the Caucasus in 2007 and dissemination to neighbouring countries emphasizes the global threat posed by ASF and further increases the risks to other countries. We review the mechanisms by which ASFV is maintained within wildlife and domestic pig populations and how it can be transmitted. We then consider the risks for global spread of ASFV and discuss possibilities of how disease can be prevented.

Download Full-text

Persistent domestic circulation of African swine fever virus in Tanzania, 2015-2017

10.21203/rs.2.15337/v4 ◽

2020 ◽

Author(s):

Clara M. Yona ◽

Merijn Vanhee ◽

Edgar Simulundu ◽

Mariam Makange ◽

Hans Nauwynck ◽

...

Keyword(s):

Phylogenetic Analysis ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Composite Likelihood ◽

Control Measures ◽

Disease Spread ◽

Hemorrhagic Disease ◽

Sylvatic Cycle ◽

East African Community ◽

Domestic Pigs

Abstract Background: African swine fever (ASF) is a highly fatal viral hemorrhagic disease of domestic pigs that threatens livelihoods and food security. In Africa, ASF virus (ASFV) circulates in sylvatic (transmission between warthogs and soft argasid ticks) and domestic (transmission between domestic pigs) cycles, with outbreaks resulting from ASFV spill-over from sylvatic cycle. A number of outbreaks were reported in different parts of Tanzania between 2015 and 2017. The present study investigated ASFV transmission patterns through viral DNA sequencing and phylogenetic analysis. A total of 3120 tissue samples were collected from 2396 domestic pigs during outbreaks at different locations in Tanzania between 2015 and 2017. Partial sequencing of the B646L (p72) gene was conducted for diagnostic confirmation and molecular characterization of ASFV. Phylogenetic analysis to study the relatedness of current ASFV with those that caused previous outbreaks in Tanzania and representatives of all known 24 ASFV was performed using the Maximum Composite Likelihood model with 1000 bootstrap replications in MEGA 6.0. Results: ASFV was confirmed to cause disease in sampled domestic pigs. ASFV genotypes II, IX, and X were detected from reported outbreaks in 2015-2017. The current ASFV isolates were similar to those recently documented in the previous studies in Tanzania. The similarities of these isolates suggests for continuous circulation of ASFV with virus maintenance within the domestic pigs. Conclusions: Genetic analysis confirmed the circulation of ASFV genotypes II, IX, and X by partial B646L (p72) gene sequencing. The similarities of current isolates to previously isolated Tanzanian isolates and pattern of disease spread suggest for continuous circulation of ASF with virus’ maintenance in the domestic pigs. Although certain viral genotypes seem to be geographically restricted into certain zones within Tanzania, genotype II seems to expand its geographical range northwards with the likelihood of spreading to other states of the East African Community. The spread of ASFV is due to breach of quarantine and transportation of infected pigs via major highways. Appropriate control measures including zoosanitary measures and quarantine enforcement are recommended to prevent ASF domestic circulation in Tanzania.

Download Full-text

Computational Analysis of African Swine Fever Virus Protein Space for the Design of an Epitope-Based Vaccine Ensemble

Pathogens ◽

10.3390/pathogens9121078 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1078 ◽

Cited By ~ 1

Author(s):

Albert Ros-Lucas ◽

Florencia Correa-Fiz ◽

Laia Bosch-Camós ◽

Fernando Rodriguez ◽

Julio Alonso-Padilla

Keyword(s):

T Cell ◽

Vaccine Development ◽

De Novo ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Economic Losses ◽

Virus Protein ◽

Hemorrhagic Disease ◽

Starting Point

African swine fever virus is the etiological agent of African swine fever, a transmissible severe hemorrhagic disease that affects pigs, causing massive economic losses. There is neither a treatment nor a vaccine available, and the only method to control its spread is by extensive culling of pigs. So far, classical vaccine development approaches have not yielded sufficiently good results in terms of concomitant safety and efficacy. Nowadays, thanks to advances in genomic and proteomic techniques, a reverse vaccinology strategy can be explored to design alternative vaccine formulations. In this study, ASFV protein sequences were analyzed using an in-house pipeline based on publicly available immunoinformatic tools to identify epitopes of interest for a prospective vaccine ensemble. These included experimentally validated sequences from the Immune Epitope Database, as well as de novo predicted sequences. Experimentally validated and predicted epitopes were prioritized following a series of criteria that included evolutionary conservation, presence in the virulent and currently circulating variant Georgia 2007/1, and lack of identity to either the pig proteome or putative proteins from pig gut microbiota. Following this strategy, 29 B-cell, 14 CD4+ T-cell and 6 CD8+ T-cell epitopes were selected, which represent a starting point to investigating the protective capacity of ASFV epitope-based vaccines.

Download Full-text

Molecular detection and characterization of African swine fever virus from field outbreaks in domestic pigs, Mizoram, India

Transboundary and Emerging Diseases ◽

10.1111/tbed.14384 ◽

2021 ◽

Author(s):

Tridib Kumar Rajkhowa ◽

J. Kiran ◽

Lalthapui Hauhnar ◽

Doris Zodinpui ◽

Amitava Paul ◽

...

Keyword(s):

Molecular Detection ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Domestic Pigs

Download Full-text

BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities

Journal of Virology ◽

10.1128/jvi.01058-17 ◽

2017 ◽

Vol 91 (21) ◽

Cited By ~ 51

Author(s):

Paula L. Monteagudo ◽

Anna Lacasta ◽

Elisabeth López ◽

Laia Bosch ◽

Javier Collado ◽

...

Keyword(s):

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Sub Saharan Africa ◽

Swine Industry ◽

Lethal Challenge ◽

Major Threat ◽

Attenuated Viruses ◽

Genotype Ii

ABSTRACT African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo. Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8+ T cells capable of recognizing both BA71 and E75 viruses in vitro. Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating. IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.

Download Full-text