Multi-country outbreak of monkeypox virus: phylogenomic characterization and signs of microevolution

Abstract The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 2022. Here, shotgun metagenomics allowed the rapid reconstruction and phylogenomic characterization of the first genome sequences of the MPXV outbreak variant. We observed that this MPXV belongs to the West African clade and that the ongoing outbreak most likely has a single origin. Although 2022 MPXV clustered with 2018–2019 cases epidemiologically linked to an endemic country, it segregates in a highly divergent phylogenetic branch (~ 50SNPs), likely representing a recent evolutionary jump. This hypermutation signature suggests the potential action of host APOBEC in viral evolution. We also detected ongoing microevolution (e.g., SNPs, minor variants and gene loss) during the human-to-human outbreak transmission, highlighting potential targets of adaptation. This study sheds light on MPXV adaptive evolution and indicates that genome sequencing might provide resolution to track the spread and transmission of this presumably slow-evolving dsDNA virus.