Genomic Diversity of Clade Ia Monkeypox Virus in the Central African Republic, 2019-2024

<b>Abstract</b>Monkeypox virus (MPXV) is a zoonotic pathogen known to be endemic to the Congo basin and West Africa, and which causes characteristic lesions disseminated on all skin surfaces of infected cases. Multiple MPXV outbreaks have been reported in the Central African Republic (CAR), a Congo basin country, at an increased frequency since 2020. The genomic history of these outbreaks in CAR is poorly characterized due to under sampling, with only a recent expansion in the number of sequences from CAR. Here, we report twenty-six new near-complete genomes from six prefectures of CAR, selected to represent outbreaks that occurred in the country between 2019 and 2024. Our analysis shows the sustained homogeneity of genomes in CAR, as all of them belonged to Clade Ia, but with an expansion of sub-lineages and therefore increased MPXV diversity within CAR. We highlight the introduction into CAR of a lineage previously known to occur only in Gabon and Cameroon, as well as the apparent regional clustering of MPXV genomes in CAR. Our analysis reveals limited APOBEC3-mediated activity, which is consistent with recent zoonotic origins and short human-to-human transmission chains observed in CAR. These analyses provide an in-depth view on the genomic diversity of MPXV in the Central African region.