Extended sequencing of vaccine and wild‐type capripoxvirus isolates provides insights into genes modulating virulence and host range

Abstract

The genus Capripoxvirus in the subfamily Chordopoxvirinae, family Poxviridae, comprises sheeppox virus (SPPV), goatpox virus (GTPV) and lumpy skin disease virus (LSDV), which cause the eponymous diseases across parts of Africa, the Middle East and Asia. These diseases cause significant economic losses and can have a devastating impact on the livelihoods and food security of small farm holders. So far, only live classically attenuated SPPV, GTPV and LSDV vaccines are commercially available and the history, safety and efficacy of many have not been well established. Here, we report 13 new capripoxvirus genome sequences, including the hairpin telomeres, from both pathogenic field isolates and vaccine strains. We have also updated the genome annotations to incorporate recent advances in our understanding of poxvirus biology. These new genomes and genes grouped phenetically with other previously sequenced capripoxvirus strains, and these new alignments collectively identified several recurring alterations in genes thought to modulate virulence and host range. In particular, some of the many large capripoxvirus ankyrin and kelch‐like proteins are commonly mutated in vaccine strains, while the variola virus B22R‐like gene homolog has also been disrupted in many vaccine isolates. Among these vaccine isolates, frameshift mutations are especially common and clearly present a risk of reversion to wild type in vaccines bearing these mutations. A consistent pattern of gene inactivation from LSDV to GTPV and then SPPV is also observed, much like the pattern of gene loss in orthopoxviruses, but, rather surprisingly, the overall genome size of ~150 kbp remains relatively constant. These data provide new insights into the evolution of capripoxviruses and the determinants of pathogenicity and host range. They will find application in the development of new vaccines with better safety, efficacy and trade profiles.

Experimental Infection and Genetic Characterization of Two Different Capripox Virus Isolates in Small Ruminants

“…This finding, together with the results of the in vivo study, support the classification of this strain in the group of the attenuated SPPV vaccines. On the other hand, GTPV-“V/103” was 100% identical to GTPV strain “India” (accession MN072620 [ 36 ]) ( Figure 3 B), which genome sequence could therefore be confirmed by our findings.…”

“…In addition, the ankyrin repeat protein genes 145 and 148 of the SPPV-“V/104” genome are truncated. Similar truncated genes 145 and 148 could be also identified in the SPPV-NISKHI vaccine strain [ 36 ]. This finding, together with the results of the in vivo study, support the classification of this strain in the group of the attenuated SPPV vaccines.…”

Comparative analysis of ankyrin (ANK) genes of five capripoxviruses isolate strains from Xinjiang province in China

“…1); another four ANK genes show no interspecies difference. Further analyzing the unique nucleotides/amino acid signatures of the interspecies difference for each ANK genes from three species of capripoxvirus, each of ANK genes have different specific nucleotide/amino acid positions, but at the same position of these characteristic sites, at least two of three species were identical, all three species of capripoxvirus with a difference is uncommon, which explained that the source of GTPV and SPPV might evolve from the LSDV missing 9 ORFs [6,26], eventually evolving three species in the process of constant generation [26]. The distribution of characteristic positions of ANK genes of five isolate strains from poxvirus in Xinjiang showed a slight difference with the previous result.…”

“…The characteristics of the ANK gene of capripoxvirus make it a potential candidate for the development of the capripox vaccine. Many live-attenuated vaccines of capripoxvirus present a common characteristic that ANK genes were disrupted with mutations [6]. Nevertheless, sporadically, this live-attenuated vaccine can cause diseases, and the vaccine fails to induce immunity [13].…”

Potential of Using Capripoxvirus Vectored Vaccines Against Arboviruses in Sheep, Goats, and Cattle

“…Although the above mentioned genes have been used to determine the species of capripoxvirus, unfortunately, the understanding of what specific genes/mutations and or gene combinations are involved in determining whether a capripoxvirus is a sheeppox, goatpox of LSDV is unknown. Analyzing the sequence information obtained from several capripoxviruses including virulent wild type and attenuated vaccines offers insight for future recombinant vaccine design (149). Understanding gene deletions found in capripoxvirus vaccines will allow strategic attenuation to target ideal virulence genes without compromising the vaccine integrity.…”