Scientists at The Pirbright Institute have shed new light on the genetics, evolution and spread of rinderpest by analysing the genetic sequences of the stocks destroyed at the Rinderpest Holding Facility and World Reference Laboratory for rinderpest held at Pirbright.
In June 2019 the final stocks of rinderpest virus (RPV) were destroyed, completing a major milestone in the World Organisation for Animal Health (OIE) and Food and Agriculture Organization of the United Nations (FAO) programme to eradicate the virus.
To ensure information about the virus that might prove useful in the future was not lost, Pirbright’s scientists led a ‘Sequence and Destroy’ project to determine the full genome sequence of all the distinct samples of RPV prior to their destruction. The results of this project have now been published in the Nature journal Scientific Reports.
“The completion of this project secures vital information about RPV and, as rinderpest is only the second viral disease to be eradicated along with smallpox, shows what can achieved with a globally coordinated effort, in this case between Pirbright scientists and our international collaborators”, said Dr Carrie Batten, Chair for the Rinderpest Holding Facility Network and Head of the Non-Vesicular Reference Laboratory at Pirbright.
A total of 121 full genomes, and another two more that lacked a short part of their sequence, were determined. After comparing all the sequences, the team found that they represent 51 different virus isolates from outbreaks and examples of three different types of vaccine strain. Bioinformatic analysis of these samples has revealed several new insights.
It was previously thought that RPVs in Africa originated from two large branches of a family tree, but the new data suggest that they can be seen as one large, disparate family, with multiple branches. The full genome sequences therefore provide evidence supporting a single entry of the virus into sub-Saharan Africa and its subsequent expansion, a pattern that is consistent with the known history of the virus in Africa.
The team also identified several different genetic mutations between groups of RPVs, one of which may have implications for how virus proteins are produced during RPV replication in infected cells. A group of Middle Eastern isolates from the 1980s and 1990s also had distinct genetic changes, which is particularly interesting because several members of this group showed high severity, with reduced time from the onset of symptoms to death compared to other strains.
Among the vaccine strains a set of related viruses that were developed originally in Korea, and weakened by growing them repeatedly in rabbits, appears to be more similar to the known African viruses than to any other Asian viruses. It remains to be determined why this is the case.
The study is an exemplar to other laboratories on how to glean as much information as possible through genetic analysis from their remaining lab samples prior to destroying them. Further bioinformatic analyses of these samples may reveal more detailed information about the growth and evolution of RPV.
This work was carried out with the financial support of the WMD Threat Reduction Program of Global Affairs Canada, the Defense Threat Reduction Agency of the United States Department of Defense, the UK Department for Environment, Food and Rural Affairs (Defra) and the UK Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI).