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Review
. 2023 Apr 18;15(4):995.
doi: 10.3390/v15040995.

Mpox Virus: Its Molecular Evolution and Potential Impact on Viral Epidemiology

Xi Yu  1   2   3 , Huicheng Shi  1   2 , Gong Cheng  1   2   4
Affiliations
Review

Mpox Virus: Its Molecular Evolution and Potential Impact on Viral Epidemiology

Xi Yu et al. Viruses. .

Abstract

Mpox (previously known as monkeypox) is an infectious viral illness caused by the mpox virus (MPXV), an orthopoxvirus that belongs to the family Poxviridae. The symptoms of mpox in humans are similar to those of smallpox, although the mortality rate is lower. In recent years, the concern over a potential global pandemic has increased due to reports of mpox spreading across Africa and other parts of the world. Prior to this discovery, mpox was a rare zoonotic disease restricted to endemic regions of Western and Central Africa. The sudden emergence of MPXV cases in multiple regions has raised concerns about its natural evolution. This review aims to provide an overview of previously available information about MPXV, including its genome, morphology, hosts and reservoirs, and virus-host interaction and immunology, as well as to perform phylogenetic analysis on available MPXV genomes, with an emphasis on the evolution of the genome in humans as new cases emerge.

Keywords: epidemiology; molecular evolution; mpox virus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic of the four infectious virion forms of poxviruses produced during the virus life cycle. IMV, intracellular mature virus; IEV, intracellular enveloped virus; CEV, cell-associated enveloped virus; EEV, extracellular enveloped virus.
Figure 2
Figure 2
Phylogenetic analysis of MPXV Clade 3 lineage A (A) and lineage B (B). Genomic sequences were downloaded from GISAID (https://gisaid.org/) (accessed on 7 December 2022) with their metadata, including the date and location that the sequences were collected. The sequences were aligned and translated by nextalign using an annotated pre-outbreak sequence (NCBI Reference Sequence: NC_063383.1, GISAID Accession ID EPI_ISL_13056282) as the reference sequence. The clade that each sequence belongs to was assigned using nucleotide substitutions defined by the Nextstrain team at https://github.com/nextstrain/monkeypox/blob/master/config/clades.tsv (accessed on 7 December 2022) [92]. A custom script was used to identify nucleotide and amino acid substitutions in each sequence compared to the reference so the date that a substitution first appeared and the frequency of the substitution in the years before the outbreak and months after the outbreak can be obtained. The aligned genomes were trimmed with trimAl for phylogenetic analysis using IQ-TREE [93,94]. The maximum likelihood trees of both Lineage A and B were inferred with the automatic ModelFinder and ultrafast bootstrap [95,96]. The resulting trees were visualized with the Interactive Tree Of Life (iTOL) [97,98].
Figure 3
Figure 3
The incidence of frequent amino acid mutations. The frequency of the appearance of SNPs in different months in 2022 was analyzed and 31 frequent non-synonymous mutations were found. The frequent amino acid mutations were clustered into four groups based on their dates of first appearance, which were determined through evolutionary analysis. The mutations located in different viral proteins are indicated by colors. The data of record numbers are sourced from Table 1.
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Publication types

Grants and funding

This work was funded by grants from the National Key Research and Development Plan of China (2021YFC2300200, 2020YFC1200104, and 2018YFA0507202), the National Natural Science Foundation of China (32188101, 81961160737, 31825001, and 81730063), the Tsinghua University Spring Breeze Fund (2020Z99CFG017), the Shenzhen Science and Technology Project (JSGG20191129144225464) and Shenzhen San-Ming Project for Prevention and Research on Vector-borne Diseases (SZSM201611064), the Innovation Team Project of Yunnan Science and Technology Department (202105AE160020), and the Yunnan Cheng Gong expert workstation (202005AF150034).

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