Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022

Abstract

Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several nonendemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV-2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV-2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 nonsynonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that 10 proteins in the MPXV are more prone to mutation, including D2L-like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L-like, OPG153, OPG188, and OPG210 proteins. In the MPXV-2022 strains, four and three nucleotide substitutions are observed in OPG105 and OPG210, respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.

Keywords: MPXV endemic; molecular evolution; monkeypox; orthopoxvirus.

Figure 1

Phylogenetic characterization of the MPXV lineage. (A) Phylogenetic analysis using FastTree of 224 isolated MPXV sequences between October 1958 to June 2022. Branches showing different lineages/clades were colored using orange (2022‐outbreak—West Africa—Clade 3—B.1), pink and black (West Africa Lineage—Clades 2 and 3), and Blue (Congo Basin lineage—Clade 1). In‐depth SNP analysis was performed to determine evolutionary trends at a nucleotide resolution. The term WA‐common refers to shared mutations within the clade; **‐specific refers to group‐specific mutations compared to the coordinate genome (NCBI: NC_063383). (B) Sequence divergence and geographical comparison map of the MPXV‐2022 outbreak sequences (updated as of June 22, 2022).

Figure 2

Characterization of the mutation of MPXV‐2022 strains. (A) Mutational analysis map of the MPXV‐2022 outbreak strains. B.1‐specific mutations were characterized and mapped based on their genomic regions (left and right variable region or core region). Nonsynonymous mutations were labeled with the protein and the mutation. APOBEC3‐like mutations were also colored red (for TC > TT mutations) and blue (for GA > AA mutations). (B) de novo mutations in the MPXV‐2022 strains. (C) Association analysis of de novo nucleotide substitutions with APOBEC3‐like in the MPXV‐2022 strains. (D) Protein annotation of de novo nucleotide substitutions in the MPXV‐2022 strains.

Figure 3

Genomic annotation of the MPXV‐2022 outbreak. (A) Illustration of previously identified MPXV protein annotations. Functions of homologous proteins are color‐coded. (B) A cumulative number of variants type greater than three times on the protein. All the protein annotations were colored accordingly, and the most variable proteins (top 10 percentile) were labeled. (C) A cumulative number of variants type 20 times more in the WA lineage at different sublineages. Genome composition changes were colored accordingly. (D) The identified protein sequence similarity between consensus outbreak sequences and other strains (MPXV‐UK‐P2, MPV‐ZAI, MVA‐BN, VAC‐COP, CPV‐GRI, and VAR‐IND).