Identification of a functional small non-coding RNA encoded by African swine fever virus

Dunn, Laura; Ivens, Alasdair; Netherton, Christopher L.; Chapman, David; Beard, Philippa M.

doi:10.1101/865147

Cited by 3 publications

(3 citation statements)

References 47 publications

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“…3a; see also Table S9 in the supplemental material); these could provide a rich hunting ground for small noncoding RNAs (sncRNAs). One TSS cluster associated with an sncRNA gene (at position 71302 on the BA71V genome) was previously reported by Dunn et al (51) as ASFVsRNA2, that is encoded in the antisense orientation relative to that of the ASFV RNA polymerase subunit RPB6-encoding gene. Further investigation of antisense sncRNAs in the BA71V transcriptome may uncover further examples of riboregulation, i.e., a more complex method of modulating its own or host gene expression beyond the protein level.…”

Section: Discussionmentioning

confidence: 76%

The African Swine Fever Virus Transcriptome

Cackett

Matelska

Sýkora

et al. 2020

J Virol

136

206

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African swine fever virus (ASFV) causes hemorrhagic fever in domestic pigs, presenting the biggest global threat to animal farming in recorded history. Despite the importance of ASFV, little is known about the mechanisms and regulation of ASFV transcription. Using RNA sequencing methods, we have determined total RNA abundance, transcription start sites, and transcription termination sites at single-nucleotide resolution. This allowed us to characterize DNA consensus motifs of early and late ASFV core promoters, as well as a polythymidylate sequence determinant for transcription termination. Our results demonstrate that ASFV utilizes alternative transcription start sites between early and late stages of infection and that ASFV RNA polymerase (RNAP) undergoes promoter-proximal transcript slippage at 5′ ends of transcription units, adding quasitemplated AU- and AUAU-5′ extensions to mRNAs. Here, we present the first much-needed genome-wide transcriptome study that provides unique insight into ASFV transcription and serves as a resource to aid future functional analyses of ASFV genes which are essential to combat this devastating disease. IMPORTANCE African swine fever virus (ASFV) causes incurable and often lethal hemorrhagic fever in domestic pigs. In 2020, ASF presents an acute and global animal health emergency that has the potential to devastate entire national economies as effective vaccines or antiviral drugs are not currently available (according to the Food and Agriculture Organization of the United Nations). With major outbreaks ongoing in Eastern Europe and Asia, urgent action is needed to advance our knowledge about the fundamental biology of ASFV, including the mechanisms and temporal control of gene expression. A thorough understanding of RNAP and transcription factor function, and of the sequence context of their promoter motifs, as well as accurate knowledge of which genes are expressed when and the amino acid sequence of the encoded proteins, is direly needed for the development of antiviral drugs and vaccines.

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Section: Discussionmentioning

confidence: 76%

The African Swine Fever Virus Transcriptome

Cackett

Matelska

Sýkora

et al. 2020

J Virol

136

206

View full text Add to dashboard Cite

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“…Ssc_circ_009380 was found to promote the activation of NF-κB pathway in the inflammatory response to TGEV by binding miR-22 [63]. Differentially expressed ln-cRNAs might be involved in inflammatory responses induced by TGEV via acting as miRNA sponges, regulating their upstream and downstream genes [64]. Data analysis based on enrichment of Gene Ontology of host target genes demonstrated that the differentially expressed miRNAs participated in regulatory networks, including cellular process, metabolic process, and immune system response [65].…”

Section: Transmissible Gastroenteritis Virus Infection and Host Ncrnasmentioning

confidence: 99%

“…Overexpression of ASFVsRNA2 led to up to a 1 log reduction in ASFV growth indicating that ASFV utilized a virally encoded small RNA to disrupt its own replication. Further study showed that ASFVsRNA2 had a variable number of 3′ U residues and it did not fit the classic miRNA biogenesis pathway, so called the canonical miRNA biogenesis pathway; therefore, ASFVs-RNA2 cannot be viewed as miRNA [64].…”

Section: Ncrnas Expressed By African Swine Fever Virusmentioning

confidence: 99%

Relationship of Noncoding RNA and Swine Viruses

Fang

Deng

2022

Intervirology

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Swine viruses are well known as a threat to the pig industry. Many signaling pathways and a number of proteins were discovered to participate in the immune responses to swine viruses. Noncoding RNAs (ncRNAs), comprising a different set of transcripts including housekeeping RNAs (for example, rRNAs and tRNAs) and regulatory RNAs (small RNAs and long non-coding RNAs), recently have been described as important regulators of viral infections regarding to swine. A growing number of studies have shown ncRNAs are an indispensable part in the responses to virus infection, involved not only in antiviral responses, but in many interactions between host and virus, some of which may benefit the certain types of swine virus. Here we review the relationship of noncoding RNA and viruses through several representative swine viruses. Further, we discuss the potential of using ncRNAs as antiviral biomarkers.

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

Dunn

Ivens

Netherton

et al. 2020

J Virol

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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.

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Identification of a functional small non-coding RNA encoded by African swine fever virus

Abstract: 10

Cited by 3 publications

References 47 publications

The African Swine Fever Virus Transcriptome

The African Swine Fever Virus Transcriptome

Relationship of Noncoding RNA and Swine Viruses

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

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