Phylogenetic Analysis of the Mpox Virus in the Sub-Saharan Africa (2022–2024)

Mpox, caused by the Mpox virus (MPXV), is a re-emerging zoonotic disease in the Poxviridae family. Since 2022, sub-Saharan Africa has experienced a resurgence of Mpox outbreaks, with the Democratic Republic of the Congo (DRC) experiencing its largest recorded outbreak. By June 2024, DRC’s MPXV cases accounted for 96% of the 567 new confirmed cases reported by the World Health Organization (WHO) across the African region. Despite MPXV’s endemicity in sub-Saharan Africa, its genetic diversity remains poorly understood. In this study, we analyzed 270 high-quality whole genome sequences from 13 African countries. The maximum likelihood method identified two principal clades: Clade I and Clade II. Clade I exhibited potential regional expansion to East Africa, while Clade II dominated in West and Southern Africa. Mutational analysis using BCF tools revealed a high frequency of non-synonymous mutations, particularly in immune-related genes and replication. Notably, we identified an enrichment of APOBEC3 mutations in Clade IIb, whereas Clade I exhibited substantially lower levels of these mutations, suggesting divergent evolutionary pressures among circulating clades, thereby highlighting the need for sustained genomic surveillance to track MPXV evolution, regional spread, and immune escape, thereby supporting real-time outbreak efforts.