Temporal Transcriptome and Promoter Architecture of the African Swine Fever Virus

Cackett, Gwenny; Matelska, Dorota; Sýkora, Michal; Portugal, Raquel; Małecki, Michał; Bähler, Jürg; Dixon, Lucas; Werner, Finn

doi:10.1101/847343

Cited by 6 publications

(2 citation statements)

References 66 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The recombination plasmid p72mCherryΔI177L was designed according to the original sequence of ASFV Georgia/2007 (3). To further add complexity to the I177L gene, a recent preprint (29) analyzing the transcriptome of ASFV, only the shortened version of I177L, as originally annotated (3), was detected as a late protein transcript, while the full-length transcript of I177L was not detected. We suggest reannotation of the I177L gene to the shortened ORF.…”

Section: Discussionmentioning

confidence: 99%

Development of a Highly Effective African Swine Fever Virus Vaccine by Deletion of the I177L Gene Results in Sterile Immunity against the Current Epidemic Eurasia Strain

Borca

Ramírez-Medina

Silva

et al. 2020

J Virol

247

238

View full text Add to dashboard Cite

African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The disease is devastating the swine industry in Central Europe and East Asia, with current outbreaks caused by circulating strains of ASFV derived from the 2007 Georgia isolate (ASFV-G), a genotype II ASFV. In the absence of any available vaccines, African swine fever (ASF) outbreak containment relies on the control and culling of infected animals. Limited cross-protection studies suggest that in order to ensure a vaccine is effective, it must be derived from the current outbreak strain or at the very least from an isolate with the same genotype. Here, we report the discovery that the deletion of a previously uncharacterized gene, I177L, from the highly virulent ASFV-G produces complete virus attenuation in swine. Animals inoculated intramuscularly with the virus lacking the I177L gene, ASFV-G-ΔI177L, at a dose range of 102 to 106 50% hemadsorbing doses (HAD50), remained clinically normal during the 28-day observational period. All ASFV-G-ΔI177L-infected animals had low viremia titers, showed no virus shedding, and developed a strong virus-specific antibody response; importantly, they were protected when challenged with the virulent parental strain ASFV-G. ASFV-G-ΔI177L is one of the few experimental vaccine candidate virus strains reported to be able to induce protection against the ASFV Georgia isolate, and it is the first vaccine capable of inducing sterile immunity against the current ASFV strain responsible for recent outbreaks. IMPORTANCE Currently, there is no commercially available vaccine against African swine fever. Outbreaks of this disease are devastating the swine industry from Central Europe to East Asia, and they are being caused by circulating strains of African swine fever virus derived from the Georgia 2007 isolate. Here, we report the discovery of a previously uncharacterized virus gene, which when deleted completely attenuates the Georgia isolate. Importantly, animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. Interestingly, ASFV-G-ΔI177L confers protection even at low doses (102 HAD50) and remains completely attenuated when inoculated at high doses (106 HAD50), demonstrating its potential as a safe vaccine candidate. At medium or higher doses (104 HAD50), sterile immunity is achieved. Therefore, ASFV-G-ΔI177L is a novel efficacious experimental ASF vaccine protecting pigs from the epidemiologically relevant ASFV Georgia isolate.

show abstract

Section: Discussionmentioning

confidence: 99%

Development of a Highly Effective African Swine Fever Virus Vaccine by Deletion of the I177L Gene Results in Sterile Immunity against the Current Epidemic Eurasia Strain

Borca

Ramírez-Medina

Silva

et al. 2020

J Virol

247

238

View full text Add to dashboard Cite

show abstract

“…ASFV transcription termination takes place at a conserved motif of seven or more consecutive thymidylate residues ( 57 ), and this poly(T) motif is retained in the mRNA ( 58 ), so it is possible this poly(U) motif is the termination signal for ASFVsRNA2 transcription. Recent detailed viral transcriptome analysis of ASFV has indicated that this motif is the termination sequence for the gene upstream of C475L, C135R ( 59 ). Therefore, it is possible ASFVsRNA2 is generated through modification of the C135R mRNA transcript or as a result of readthrough transcription of this transcript.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Functional Small Noncoding RNA of African Swine Fever Virus

Dunn

Ivens

Netherton

et al. 2020

J Virol

View full text Add to dashboard Cite

African swine fever virus (ASFV) causes a lethal haemorrhagic disease of domestic pigs, against which there is no vaccine available. ASFV has a large, double-stranded DNA genome that encodes over 150 proteins. Replication takes place predominantly in the cytoplasm of the cell and involves complex interactions with host cellular components including small non-coding RNAs (sncRNAs). A number of DNA viruses are known to manipulate sncRNA either by encoding their own or disrupting host sncRNA. In order to investigate the interplay between ASFV and sncRNAs, a study of host and viral small RNAs extracted from ASFV-infected primary porcine macrophages (PAMs) was undertaken. We discovered that ASFV infection had only a modest effect on host miRNAs, with only 6 miRNAs differentially expressed during infection. The data also revealed 3 potential novel small RNAs encoded by ASFV, ASFVsRNA1-3. Further investigation of ASFVsRNA2 detected it in lymphoid tissue from pigs with ASF. Overexpression of ASFVsRNA2 led to up to a 1 log reduction in ASFV growth indicating that ASFV utilises a virally-encoded small RNA to disrupt its own replication. IMPORTANCE African swine fever (ASF) poses a major threat to pig populations and food security worldwide. The disease is endemic in Africa and Eastern Europe and rapidly emerging into Asia where it has led to the deaths of over a million pigs in the last 12 months. The development of safe and effective vaccines to protect pigs against ASF has been hindered by lack of understanding of the complex interactions between ASFV and the host cell. We focused our work on characterising the interactions between ASFV and sncRNAs. Although comparatively modest changes to host sncRNA abundances were observed upon ASFV infection, we discovered and characterised a novel functional ASFV-encoded sncRNA. The results from this study add important insights into ASFV host-pathogen interactions. This knowledge may be exploited to develop more effective ASFV vaccines that take advantage of the sncRNA system.

show abstract

Potential m6A and m5C Methylations within the Genome of A Chinese African Swine Fever Virus Strain

et al. 2020

View full text Add to dashboard Cite

Temporal Transcriptome and Promoter Architecture of the African Swine Fever Virus

Cited by 6 publications

References 66 publications

Development of a Highly Effective African Swine Fever Virus Vaccine by Deletion of the I177L Gene Results in Sterile Immunity against the Current Epidemic Eurasia Strain

Development of a Highly Effective African Swine Fever Virus Vaccine by Deletion of the I177L Gene Results in Sterile Immunity against the Current Epidemic Eurasia Strain

Identification of a Functional Small Noncoding RNA of African Swine Fever Virus

Potential m6A and m5C Methylations within the Genome of A Chinese African Swine Fever Virus Strain

Contact Info

Product

Resources

About