Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus

• Published in: Nature medicine Vol. 28; no. 8; pp. 1569 - 1572
• Main Authors: Isidro, Joana, Borges, Vítor, Pinto, Miguel, Sobral, Daniel, Santos, João Dourado, Nunes, Alexandra, Mixão, Verónica, Ferreira, Rita, Santos, Daniela, Duarte, Silvia, Vieira, Luís, Borrego, Maria José, Núncio, Sofia, de Carvalho, Isabel Lopes, Pelerito, Ana, Cordeiro, Rita, Gomes, João Paulo
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-08-2022; Nature Publishing Group
• Subjects: 631/326/325/2483; 692/699/255/2514; Biomedical and Life Sciences; Biomedicine; Brief Communication; Cancer Research; Disease Outbreaks; Divergence; DNA viruses; Evolution; Gene sequencing; Genomes; Humans; Infectious Diseases; Metabolic Diseases; Metagenomics; Molecular Medicine; Monkeypox; Monkeypox virus - genetics; Mpox (monkeypox) - epidemiology; Mpox (monkeypox) - genetics; Neurosciences; Nucleotide sequence; Orthopoxvirus; Outbreaks; Phylogeny; Viruses
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-022-01907-y

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.
Analysis of the first sequences from the 2022 multi-country outbreak of monkeypox virus shows relatedness and substantial divergence from a 2018–2019 outbreak, suggesting rapid virus evolution with possible implications for human-to-human transmission.