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Genomic characterization and molecular evolution of human monkeypox viruses

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Abstract

Monkeypox virus is a member of the family Poxviridae, as are variola virus and vaccinia virus. It has a linear double-strand DNA genome approximately 197 kb long, containing ~190 non-overlapping ORFs. Comparison of members of the Central and West African clades shows the presence of unique genes that are associated with different disease presentations, depending on the strain. The last smallpox vaccination efforts ended in the mid-1980s, and there is concern about the recent spread of human monkeypox disease around the world. Almost 87,000 human monkeypox cases have been diagnosed in the world, of which more than 10,900 were in Brazil. The aim of this study was to evaluate the epidemiology and molecular evolution of hMpxV. From computational biology analysis of 640 hMpxV genomes from 1962 to 2022, synteny breaks and gene conservation were observed between Central and West clade genomes, and strains belonged with the 2022 outbreak assigned to the West African clade. Evidence was found for diversifying selective pressure at specific sites within protein coding sequences, acting on immunomodulatory processes. The existence of different sites under diversifying and purifying selection in paralog genes indicates adaptive mechanisms underlying the host-pathogen interaction of monkeypox virus in humans.

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Data availability

Full tables acknowledging the authors and corresponding labs submitting sequencing data used in this study can be found in Online Resource 8. Additional information used and/or analyzed during the current study is available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Dr. Mark Thompson for reviewing the English writing.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil

    Patrícia Aline Gröhs Ferrareze

  2. Sociedade Brasileira de Valorização das Sociedades Médicas (SOBEMED), São Paulo, Brazil

    Rute Alves Pereira e Costa

  3. Department of Pharmacosciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), 245/200C Sarmento Leite St, Porto Alegre, RS, 90050-170, Brazil

    Claudia Elizabeth Thompson

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Contributions

PAGF and CET conceived the idea, designed the study, and performed all data analysis, investigation, and original draft preparation. PAGF, CET, and RAPC performed the manuscript review and editing. All authors have read and approved the manuscript.

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Correspondence to Claudia Elizabeth Thompson.

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Supplementary Information

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705_2023_5904_MOESM1_ESM.pdf

Online Resource 1 Genomic alignment between Central African clade sequence DQ011155.1 (human monkeypox virus strain Zaire_1979-005) and West African clade sequence NC_063383.1 (human monkeypox virus strain M5312_HM12_Rivers). Identity indicates synteny conservation between genomic blocks, which are colored in gray (syntenic) or black (non-syntenic). Annotated genes are colored in red and labeled. Predicted ORFs are colored in yellow. Genes with sites under positive selection pressure are highlighted in light red boxes

Online Resource 2 Predicted ORFs for absent genes in West and Central Africa genomes

705_2023_5904_MOESM3_ESM.pdf

Online Resource 3 Gene identification correspondence from sequences with positively selected sites in orthogroups shared between monkeypox virus, vaccinia virus, and variola virus genomes

705_2023_5904_MOESM4_ESM.png

Online Resource 4 Synteny conservation between Central African clade sequence DQ011155.1 (human monkeypox virus strain Zaire_1979-005) and West African clade sequence NC_063383.1 (human monkeypox virus strain M5312_HM12_Rivers) for AAY97205 (A) and AAY97367 (B) sequence regions. Block colors indicate synteny conservation (pink), partial conservation (red), and synteny break (white). White horizontal bars indicate annotated genes. Blue arrows indicate predicted ortholog ORFs

705_2023_5904_MOESM5_ESM.xlsx

Online Resource 5 Sites identified as being under positive and negative selective pressure by the FUBAR and FEL method, respectively, for monkeypox virus genes and their associated biological processes

705_2023_5904_MOESM6_ESM.xlsx

Online Resource 6 Sites identified as being under positive and negative selective pressure for monkeypox virus genes of 2022 outbreak genomes by FUBAR and FEL methods

705_2023_5904_MOESM7_ESM.pdf

Online Resource 7 Maximum-likelihood phylogenetic tree based on 155 concatenated monkeypox virus gene alignments. (A) Partitioned tree. (B) Non-partitioned best-fit tree generated with TempEst software by evaluation of the sequence's temporal signal

Online Resource 8 GISAID acknowledgment list for monkeypox virus genomes selected for this stud

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Ferrareze, P.A.G., Pereira e Costa, R.A. & Thompson, C.E. Genomic characterization and molecular evolution of human monkeypox viruses. Arch Virol 168, 278 (2023). https://doi.org/10.1007/s00705-023-05904-5

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