The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 2022^1-6. Here, shotgun metagenomics allowed the rapid reconstruction and phylogenomic characterization of the first MPXV outbreak genome sequences, showing that this MPXV belongs to clade 3 and that the outbreak most likely has a single origin. Although 2022 MPXV (lineage B.1) clustered with 2018-2019 cases linked to an endemic country, it segregates in a divergent phylogenetic branch, likely reflecting continuous accelerated evolution. An in-depth mutational analysis suggests the action of host APOBEC3 in viral evolution as well as signs of potential MPXV human adaptation in ongoing microevolution. Our findings also indicate that genome sequencing may provide resolution to track the spread and transmission of this presumably slow-evolving dsDNA virus.

2022 年 5 月确定了迄今为止在非流行国家发生的最大规模猴痘病毒 (MPXV) 疫情^1-6. 在这里，鸟枪法宏基因组学允许快速重建和系统基因组学表征第一次猴痘病毒爆发的基因组序列，表明该猴痘病毒属于进化枝 3，并且爆发很可能具有单一起源。尽管 2022 年猴痘病毒（谱系 B.1）与 2018-2019 年与流行国家相关的病例聚集在一起，但它分离在不同的系统发育分支中，可能反映了持续加速的进化。深入的突变分析表明宿主 APOBEC3 在病毒进化中的作用以及在正在进行的微进化中潜在的 MPXV 人类适应的迹象。我们的研究结果还表明，基因组测序可以提供分辨率来跟踪这种可能进化缓慢的 dsDNA 病毒的传播和传播。