Full genome sequencing of archived wild type and vaccine rinderpest virus isolates prior to their destruction

Abstract

When rinderpest virus (RPV) was declared eradicated in 2011, the only remaining samples of this once much-feared livestock virus were those held in various laboratories. in order to allow the destruction of our institute's stocks of RpV while maintaining the ability to recover the various viruses if ever required, we have determined the full genome sequence of all our distinct samples of RPV, including 51 wild type viruses and examples of three different types of vaccine strain. Examination of the sequences of these virus isolates has shown that the African isolates form a single disparate clade, rather than two separate clades, which is more in accord with the known history of the virus in Africa. We have also identified two groups of goat-passaged viruses which have acquired an extra 6 bases in the long untranslated region between the M and f protein coding sequences, and shown that, for more than half the genomes sequenced, translation of the f protein requires translational frameshift or non-standard translation initiation. curiously, the clade containing the lapinised vaccine viruses that were developed originally in Korea appears to be more similar to the known African viruses than to any other Asian viruses.Rinderpest (RP) was one of the most severe diseases of cattle ever recorded, with high morbidity rates, and mortality rates of 80% to 90% in naïve populations. The disease was declared eradicated in 2011 1 , thus becoming the second viral disease, after smallpox, to be eradicated, with global benefits estimated to be in the billions of dollars 2 . The RP virus (RPV) itself has not been entirely eliminated, with a number of laboratories known to have samples of wild type RPV. Accidental release of RPV from such a laboratory is thought to be the most likely pathway by which the virus might re-enter the environment 3,4 , although it might also be deliberately released as an act of sabotage or bioterrorism. The member states of the World Organisation for Animal Health (OIE), and the Food and Agricultural Organisation of the United Nations (FAO) agreed to restrict all work with the virus and to allow the storage of the virus only in highly secure Rinderpest Holding Facilities (RHFs) that have been inspected and approved jointly by OIE and FAO.The FAO-OIE RHF in the UK is the Pirbright Institute which, as the Institute for Animal Health, and before that the Animal Virus Research Institute, was a centre for research on RPV since the 1960s. The institute developed the monoclonal antibody-based competition ELISA (cELISA) used extensively for surveillance 5 , as well as the most widely used RT-PCR assay for RPV 6 and the concept of different geographic lineages of the virus based on the sequence of the product from the RT-PCR 7 . The first RPV genome sequences were determined at Pirbright 8,9 and the system for recovering RPV from a cDNA copy of the genome was developed there 10 . Because of this history, and its links to many of the countries where RPV was still endemic in the latter half of the 20 th century, t...

Molecular epidemiology of peste des petits ruminants virus emergence in critically endangered Mongolian saiga antelope and other wild ungulates

“…that genome length is a multiple of six, which is necessary for efficient replication of members of the Paramyxoviridae family ( Calain and Roux 1993 ). Interestingly, similar insertions have also been observed in MeV and rinderpest virus genomes ( Bankamp et al, 2014 ; Ivancic-Jelecki et al, 2016 ; Gil et al, 2018 ; King et al., 2020 ). Since the PPRV-F 5ʹ UTR is known to enhance F gene translation ( Chulakasian et al, 2013 ), experiments to address the functional consequences, and potential selective advantage, of the observed insertion in the Mongolian and Chinese PPRV should be prioritised.…”

Molecular epidemiology of peste des petits ruminants virus emergence in critically endangered Mongolian saiga antelope and other wild ungulates

“…Insertions in measles virus genomes are thought to arise via polymerase slippage errors when transcribing homopolymeric regions [58], suggesting a similar mechanism may have occurred in an ancestor to the 2013 China PPRV clade, and the resulting insertion has been maintained in the Mongolian PPRV. Interestingly, six nucleotide insertions in the 5’UTR of the F gene were also reported in goat-adapted rinderpest virus vaccine strains [59]. Similarly, several variants of measles virus have been identified with a net gain of six nucleotides within the M-F UTR and possibly associated with lineage emergence [60, 61].…”

Transboundary Animal Diseases, an Overview of 17 Diseases with Potential for Global Spread and Serious Consequences

“…Some labs have participated in a program called "sequence and destroy", launched by the FAO and OIE in 2015 [564]. Full genome sequencing allows destruction of virus stocks while maintaining the ability to recover virus if needed [568]. Ironically, the advances in synthetic biology that made destruction more palatable may have raised the risk of reintroduction [569].…”