Emergence and diversity of monkeypox virus Clade IIb sub-lineages in Nigeria (1971-2023) and its role in the 2022 global outbreak.

Abstract

The exact role played by Nigeria in the global monkeypox virus (MPXV) outbreak of 2022 remains unclear, despite exported cases to Singapore, the United Kingdom (UK), the United States of America (USA), and Israel from 2018 to 2022. We sought to resolve the origin of the 2022 MPXV global outbreak. All Nigerian MPXV whole genomes deposited in the EpiPox™ database were aligned using Nextclade v3.13.3 against the reference genome (NC_063383.1) for lineage and mutation analyses. Multiple sequence alignments were performed using MAFFT version 7, followed by maximum likelihood trees in IQ-TREE for clades A.3 and B.1 and visualised in iTOL viewer. We quantified total C → T substitutions as APOBEC3-related mutations. Seven clades or sub-lineages, namely: A (2017-2023), A.1 (2018 and 2019), A.2 and A.3 (2019), A.2.2 (2022), A.2.3 (2022 and 2023), and B.1 (2022) were observed. There was a gradual buildup of total substitution events (APOBEC3-related mutations) from 1978 to 2023, with a slight decline in 2020 but most pronounced in 2019, 2021, and 2022. Furthermore, total substitutions events were widespread across both variable and core regions of the MPXV genomes. The B.1 and A.3 maximum likelihood trees points to Nigerian ancestral roots, supporting our hypothesis that the B.1 sub-lineage originated in Nigeria. Our phylodynamics analyses showed peak distributions for the A.3 clade around 2013, while that of B.1 showed rapid spread of the virus in May 2022. The evolution rates of the for A.3 and B.1 were 6.94 × 10and ∼ 3.091 × 10substitutions/site/year, while their molecular clock signals were moderate with respective values of R = 0.56 and 0.56. Overall, our findings indicate that the B.1 sub-lineage, which triggered the 2022 outbreak, potentially evolved from A.3, with both lineages having their ancestral roots in Nigeria.