African swine fever virus – variants on the rise

African swine fever virus (ASFV), a large and complex DNA-virus circulating between soft ticks and indigenous suids in sub-Saharan Africa, has made its way into swine populations from Europe to Asia. This virus, causing a severe haemorrhagic disease (African swine fever) with very high lethality rates in wild boar and domestic pigs, has demonstrated a remarkably high genetic stability for over 10 years. Consequently, analyses into virus evolution and molecular epidemiology often struggled to provide the genetic basis to trace outbreaks while few resources have been dedicated to genomic surveillance on whole-genome level. During its recent incursion into Germany in 2020, ASFV has unexpectedly diverged into five clearly distinguishable linages with at least ten different variants characterized by high-impact mutations never identified before. Noticeably, all new variants share a frameshift mutation in the 3’ end of the DNA polymerase PolX gene O174L, suggesting a causative role as possible mutator gene. Although epidemiological modelling supported the influence of increased mutation rates, it remains unknown how fast virus evolution might progress under these circumstances. Moreover, a tailored Sanger sequencing approach allowed us, for the first time, to trace variants with genomic epidemiology to regional clusters. In conclusion, our findings suggest that this new factor has the potential to dramatically influence the course of the ASFV pandemic with unknown outcome. Therefore, our work highlights the importance of genomic surveillance of ASFV on whole-genome level, the need for high-quality sequences and calls for a closer monitoring of future phenotypic changes of ASFV.非洲猪瘟病毒（African swine fever virus, ASFV）是一种大型复杂的DNA病毒，在撒哈拉以南非洲的软蜱与本土猪科动物之间循环传播，现已传入欧洲至亚洲的猪群中。该病毒可引发严重的出血性疾病——非洲猪瘟，在野猪与家猪中致死率极高，且十余年来展现出极高的遗传稳定性。因此，针对病毒演化与分子流行病学的分析往往难以提供追踪疫情暴发的遗传学依据，而针对全基因组层面的基因组监测相关研究资源也相对匮乏。2020年该病毒传入德国后，ASFV意外分化出5个可清晰区分的谱系，以及至少10种不同变异株，其特征为此前从未被发现的高影响突变。值得注意的是，所有新型变异株均在DNA聚合酶PolX基因O174L的3'末端携带一处移码突变，提示该突变可能作为诱变基因发挥致病作用。尽管流行病学模型支持突变率升高的影响，但目前仍不清楚在这种情况下病毒演化的速度会有多快。此外，我们首次通过定制化的桑格（Sanger）测序方法，借助基因组流行病学追踪到了区域性聚集的变异株。综上，我们的研究结果表明，这一新的变异因素可能会极大地影响非洲猪瘟疫情的发展趋势，其结局尚不可知。因此，本研究强调了针对ASFV开展全基因组层面基因组监测的重要性、高质量病毒基因组序列的必要性，并呼吁对ASFV未来的表型变化进行更密切的监测。