Isidro, JoanaBorges, VítorPinto, MiguelSobral, DanielSantos, João DouradoNunes, AlexandraMixão, VerónicaFerreira, RitaSantos, DanielaDuarte, SilviaVieira, LuísBorrego, Maria JoséNúncio, Sofiade Carvalho, Isabel LopesPelerito, AnaCordeiro, RitaGomes, João Paulo2023-01-302023-01-302022-08Nat Med. 2022 Aug;28(8):1569-1572. doi: 10.1038/s41591-022-01907-y. Epub 2022 Jun 24.1078-8956http://hdl.handle.net/10400.18/8471Trabalho distinguido com o Prémio João Monjardino 2022.https://www.insa.min-saude.pt/investigadora-do-instituto-ricardo-jorge-vence-premio-joao-monjardino-2022/s41591-022-02036-2_Erratum in: Nat Med. 2022 Oct;28(10):2220-2221. doi: 10.1038/s41591-022-02036-2.The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 2022 (refs. 1-6). In this study, 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 double-stranded DNA virus.engMonkeypoxMonkeypox VirusMonkeypox / geneticsMonkeypox / epidemiologyPhylogenyZoonotic DiseaseDisease OutbreaksHumansInfecções Sistémicas e Zoonosesjournal article10.1038/s41591-022-01907-y