Department of Medical Microbiology and Immunology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.
Department of Agricultural, Food, and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada.
Transbound Emerg Dis. 2020 Jan;67(1):80-97. doi: 10.1111/tbed.13322. Epub 2019 Aug 30.
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.
在痘病毒科的 Chordopoxvirinae 亚科中，有绵羊痘病毒（SPPV）、山羊痘病毒（GTPV）和牛结节性皮肤病病毒（LSDV）三个属，它们分别导致同名疾病，在非洲、中东和亚洲部分地区流行。这些疾病会造成巨大的经济损失，对小农场主的生计和粮食安全产生毁灭性影响。到目前为止，只有经典减毒的 SPPV、GTPV 和 LSDV 疫苗可用于商业用途，其历史、安全性和有效性尚未得到充分证实。在此，我们报告了来自致病性田间分离株和疫苗株的 13 个新的羊痘病毒基因组序列，包括发夹状端粒。我们还更新了基因组注释，纳入了痘病毒生物学研究的最新进展。这些新的基因组和基因与其他已测序的羊痘病毒株在表型上聚类，这些新的比对共同确定了几个与毒力和宿主范围相关的基因的反复改变。特别是，一些大型羊痘病毒锚蛋白和 Kelch 样蛋白在疫苗株中经常发生突变，而天花病毒 B22R 样基因同源物在许多疫苗分离株中也被破坏。在这些疫苗分离株中，移码突变尤其常见，携带这些突变的疫苗明显存在回复为野生型的风险。从 LSDV 到 GTPV 再到 SPPV，也观察到基因失活的一致模式，与正痘病毒的基因丢失模式非常相似，但令人惊讶的是，约 150kbp 的整体基因组大小保持相对恒定。这些数据为羊痘病毒的进化以及毒力和宿主范围的决定因素提供了新的见解。它们将应用于开发具有更好安全性、有效性和贸易特征的新型疫苗。
