Scientists from The Pirbright Institute have worked with UCL to map the expression of genes across the entire African swine fever virus (ASFV) genome, which has helped to establish their order of activation as well as uncovering new genes. The research could provide vital information for those developing vaccines and antiviral drugs to prevent the deadly pig disease caused by this virus.
In their study, published in the Journal of Virology, the researchers used next generation sequencing to analyse genes expressed by ASFV. From this they created the first complete genetic road map, which reveals the order that different sets of ASFV genes are turned on throughout its infection cycle.
Genes, including those in ASFV, are activated through a process called transcription. This is carried out by a molecular machine called RNA polymerase, which serves as ‘gatekeeper’ by ensuring that the information coded in the DNA is expressed at the correct time during infection. The RNA polymerase finds genes based on specific DNA sequences, or ‘promoters’, that are located before a gene.
The team demonstrated that genes expressed during early infection have different promoters to those expressed later, allowing the virus to shift the pattern of activated genes according to the stage of infection. Genes used for DNA replication and immune system evasion are switched on early in the infection cycle, whereas those involved in creating proteins for the new virus particles are activated later.
“ASFV has a very large DNA genome. For comparison, the influenza virus expresses eight genes, whereas ASFV expresses between 150 and 190, which has so far made it difficult for scientists to identify and determine the significance of each gene. Our study helps to untangle which genes are important during different stages of infection to better understand their functions”, said Dr Linda Dixon, Head of the African Swine Fever Virus Group at Pirbright.
“Our data shows ASFV has a complex and mammalian-like method for controlling gene expression, that uses specific promoters to enable RNA polymerase to differentiate between which genes it should express when during viral infection. Our study has also uncovered over 30 novel genes that were previously unknown”, said Finn Werner, Professor of Molecular Biophysics at UCL.
Major African swine fever outbreaks continue to spread across Eastern Europe, Asia and Africa, which in 2019 resulted in the death of nearly seven million pigs. By advancing knowledge of ASFV fundamental biology, this study provides vital information that will help to progress research into desperately needed disease control methods.
Notes to editors:
ASFV causes an often lethal haemorrhagic fever in domestic pigs and wild boar. Effective vaccines or antiviral drugs are not available for ASFV, therefore biosecurity measures are essential for outbreak prevention.
Researchers at Pirbright are currently developing different types of ASF vaccines (a live attenuated vaccine and a subunit vaccine) with the aim of producing one that will protect pigs from this deadly disease. They are also working with ViroVet to produce ASF antivirals that could lower virus replication in pigs and limit clinical signs, which would form an important part of any feed-based strategy to control the virus.
The RNAP laboratory at UCL works on the structure, function and evolution of transcription machineries in a range of model organisms including viruses. Importantly, the ASFV RNA polymerase shows surprising similarities but also marked differences to other systems including the Archaea, a domain of life that is thought to be ancestral to all complex life on earth.
This research was funded by Wellcome.
Chris Lane, Media Relations Manager
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About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council, part of UK Research and Innovation (BBSRC UKRI), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
With an annual income in excess of £35 million from grants and commercial activity, and a total of £12.6 million strategic investment from BBSRC during 2018-2019, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
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