Sequestration and Destruction of Rinderpest Virus–Containing Material 10 Years after Eradication

In 2021, the world marked 10 years free from rinderpest. The United Nations Food and Agriculture Organization and World Organisation for Animal Health have since made great strides in consolidating, sequencing, and destroying stocks of rinderpest virus–containing material, currently kept by only 14 known institutions. This progress must continue.

This study used a replication-defective vesicular stomatitis virus based pseudotyping system to measure neutralizing antibodies against RPV and PPR. This system does not require the use of live infectious viral materials and thus mitigates the risk of accidental exposure. Analysis revealed that individuals vaccinated for RPV also are protected against PPR infection. Individuals that were vaccinated against PPR had lower antibody titers than those who were naturally infected and in individuals infected with either PPR or RPV neutralizing responses were highest against the homologous virus. This indicates that retrospective analysis of serologic samples can be used to determine the pathogen to which an infected individual was exposed. Because of the request to destroy all RPV samples following eradication a new diagnostic method must be developed that does not rely on RPV as a positive material. Newcastle Disease with small RNA inserts based on RPV or PPV was used as a positive control for extraction, reverse transcription, and amplification.

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Enzyme activity The V proteins of RPV, measles virus, PPR, and canine distemper were compared to determine which had the ability to block type 1 and type 2 interferon action. Analysis revealed that the V proteins of each morbillivirus could block type 1 interferon action but they had varying abilities to block type 2 interferon action which is correlated with the co-precipitation of STAT1 with the V protein. Further analysis revealed that all morbillivirus V proteins form a complex with Tyk2 and Jak2, two interferon-receptor-associated kinases.
Pirbright, UK* 8 The enzymatic role of RPV V protein was investigated to determine how it blocks interferon signaling. Analysis revealed that the morbillivirus V proteins have at least three functions that inhibit interferon signaling, the binding of STAT1 also seen with P and W proteins) which enables the blockade of type 2 interferon signaling, the binding of STAT1 which requires the Vs domain and Pirbright, United Kingdom* Study category Summary Lab location Reference part of the W domain, and the association with interferon receptor-associated kinases which also requires the Vs domain.
Partially purified recombinant RNA polymerase complex of RPV was used to show in vitro methylation of capped mRNA. Analysis revealed that the catalytic module for cap 0 methyl transferase activity is located in domain 3 of the L protein whereas domain 2 stabilizes the enzyme and increases catalytic efficiency. This provides support for the modular nation of the RPV L protein.
Bangalore, India § 10 E. coli was used to express the RTPase domain of RPV to investigate the RTPase activity of L protein. Analysis revealed that L protein exhibits RTPase and NTPase activities and that it has a two-metal mechanism similar to the RTPase domain of other viruses.
Bangalore, India § 11 E. coli was used to express the RTPase domain of RPV to investigate its enzymatic abilities. Analysis revealed that the L protein of RPV has RNAdependent RNA polymerase, RTPase, Guanylyltransferase (GTase), and Methyltransferase activity in addition to pyrophosphatase (Ppase) and tripolyphosphatase (PPPase) activity.

Bangalore, India § 12
Genome sequencing The B and L strains of RPV were sequenced to investigate host range and virulence factors. The stock B strain is pathogenic to cattle whereas the L strain is pathogenic to rabbits but not cattle and buffalo. Analysis revealed that differences in pathogenicity to cattle is caused by nt/aa substitution in P/C/V genes.
Tokyo, Japan* 13 The LATC06 strain of RPV was sequenced and compared to other rinderpest viral strains. Analysis revealed that the functions of the LATC06 (Korea) and LA (Japan) strains of RPV are similar with regards to immunodominance in humoral immunity.

Anyang, Korea 14
The genomes of three strains of RPV, L72, LA77, and LA96, were sequenced and analyzed to investigate their genetic variability. Analysis revealed that genetic variability occurs within the vaccine virus strain and that amino acid sequence similarity between Fusan and other strains was the lowest within the P, C, and V proteins. This indicated that the difference in pathogenicity of different strains may be Because of the V protein.

Anyang, Korea 15
The LA-AKO strain of the RPV vaccine was sequenced. Analysis revealed that the bulk vaccine comprises mixed viral populations with minor mutations at the nucleotide level.
Ibaraki, Japan*, ‡ 16 In preparation for the destruction of all RPV samples, the full genome sequence was determined of each distinct RPV sample housed at Pirbright. Analysis revealed that the African isolates form a single disparate clade as opposed to two separate clades and that the clade containing viruses developed in Korea were more similar to African viruses than Asian viruses.

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*Conducted in association with a current FAO-WOAH designated RHF †Presented research conducted before 2011 ‡Supported by the FAO-WOAH Joint Advisory Committee for Rinderpest. §Rinderpest virus containing material (RVCM) was not used in these studies.