1887

Microbial Genomics logo

Volume 9, Issue 4

Monkeypox virus: phylogenomics, host–pathogen interactome and mutational cascade Open Access

Abstract

While the world is still recovering from the Covid-19 pandemic, monkeypox virus (MPXV) awaits to cause another global outbreak as a challenge to all of mankind. However, the Covid-19 pandemic has taught us a lesson to speed up the pace of viral genomic research for the implementation of preventive and treatment strategies. One of the important aspects of MPXV that needs immediate insight is its evolutionary lineage based on genomic studies. Utilizing high-quality isolates from the GISAID (Global Initiative on Sharing All Influenza Data) database, primarily sourced from Europe and North America, we employed a SNP-based whole-genome phylogeny method and identified four major clusters among 628 MPXV isolates. Our findings indicate a distinct evolutionary lineage for the first MPXV isolate, and a complex epidemiology and evolution of MPXV strains across various countries. Further analysis of the host–pathogen interaction network revealed key viral proteins, such as E3, SPI-2, K7 and CrmB, that play a significant role in regulating the network and inhibiting the host’s cellular innate immune system. Our structural analysis of proteins E3 and CrmB revealed potential disruption of stability due to certain mutations. While this study identified a large number of mutations within the new outbreak clade, it also reflected that we need to move fast with the genomic analysis of newly detected strains from around the world to develop better prevention and treatment methods.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): host–protein interaction , MPXV , mutations , orthopoxvirus and phylogeny
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000987
2023-04-12
2024-05-04
Loading full text...

Full text loading...

/deliver/fulltext/mgen/9/4/mgen000987.html?itemId=/content/journal/mgen/10.1099/mgen.0.000987&mimeType=html&fmt=ahah

References

  1. Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ 1972; 46:593–597 [PubMed]
     [Google Scholar]
  2. Sklenovská N, Van Ranst M. Emergence of monkeypox as the most important orthopoxvirus infection in humans. Front Public Health 2018; 6:241 [View Article] [PubMed]
     [Google Scholar]
  3. Anand S, Hallsworth JE, Timmis J, Verstraete W, Casadevall A et al. Weaponising microbes for peace. Microb Biotechnol 2023 [View Article]
     [Google Scholar]
  4. Diaz-Cánova D, Mavian C, Brinkmann A, Nitsche A, Moens U et al. Genomic sequencing and phylogenomics of cowpox virus. Viruses 2022; 14:2134 [View Article] [PubMed]
     [Google Scholar]
  5. Senkevich TG, Yutin N, Wolf YI, Koonin EV, Moss B. Ancient gene capture and recent gene loss shape the evolution of orthopoxvirus-host interaction genes. mBio 2021; 12:e0149521 [View Article] [PubMed]
     [Google Scholar]
  6. Vaughan A, Aarons E, Astbury J, Brooks T, Chand M et al. Human-to-human transmission of monkeypox virus. Emerg Infect Dis 2020; 26:782–785 [View Article]
     [Google Scholar]
  7. Adler H, Gould S, Hine P, Snell LB, Wong W et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis 2022; 22:1153–1162 [View Article] [PubMed]
     [Google Scholar]
  8. Kumar R, Verma H, Singhvi N, Sood U, Gupta V et al. Comparative genomic analysis of rapidly evolving SARS-CoV-2 reveals mosaic pattern of phylogeographical distribution. mSystems 2020; 5:e00505-20 [View Article] [PubMed]
     [Google Scholar]
  9. Gupta V, Haider S, Verma M, Singhvi N, Ponnusamy K et al. Comparative genomics and integrated network approach unveiled undirected phylogeny patterns, co-mutational hot spots, functional cross talk, and regulatory interactions in SARS-CoV-2. mSystems 2021; 6:e00030-21 [View Article] [PubMed]
     [Google Scholar]
  10. Gurevich A, Saveliev V, Vyahhi N, Tesler G. QUAST: quality assessment tool for genome assemblies. Bioinformatics 2013; 29:1072–1075 [View Article] [PubMed]
     [Google Scholar]
  11. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
     [Google Scholar]
  12. Gardner SN, Slezak T, Hall BG. kSNP3.0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome. Bioinformatics 2015; 31:2877–2878 [View Article] [PubMed]
     [Google Scholar]
  13. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 2021; 49:W293–W296 [View Article] [PubMed]
     [Google Scholar]
  14. Löytynoja A. Phylogeny-aware alignment with PRANK. Methods Mol Biol 2014; 1079:155–170 [View Article] [PubMed]
     [Google Scholar]
  15. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article] [PubMed]
     [Google Scholar]
  16. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol 2020; 37:1530–1534 [View Article] [PubMed]
     [Google Scholar]
  17. Contreras-Moreira B, Vinuesa P. GET_HOMOLOGUES, a versatile software package for scalable and robust microbial pangenome analysis. Appl Environ Microbiol 2013; 79:7696–7701 [View Article] [PubMed]
     [Google Scholar]
  18. Pond SLK, Frost SDW, Muse SV. HyPhy: hypothesis testing using phylogenies. Bioinformatics 2005; 21:676–679 [View Article] [PubMed]
     [Google Scholar]
  19. Weaver S, Shank SD, Spielman SJ, Li M, Muse SV et al. Datamonkey 2.0: a modern web application for characterizing selective and other evolutionary processes. Mol Biol Evol 2018; 35:773–777 [View Article] [PubMed]
     [Google Scholar]
  20. Hongo JA, de Castro GM, Cintra LC, Zerlotini A, Lobo FP. POTION: an end-to-end pipeline for positive Darwinian selection detection in genome-scale data through phylogenetic comparison of protein-coding genes. BMC Genomics 2015; 16:567 [View Article] [PubMed]
     [Google Scholar]
  21. Li L, Stoeckert CJ Jr, Roos DS. OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Res 2003; 13:2178–2189 [View Article] [PubMed]
     [Google Scholar]
  22. Bruen TC, Philippe H, Bryant D. A simple and robust statistical test for detecting the presence of recombination. Genetics 2006; 172:2665–2681 [View Article] [PubMed]
     [Google Scholar]
  23. Capella-Gutiérrez S, Silla-Martínez JM, Gabaldón T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 2009; 25:1972–1973 [View Article] [PubMed]
     [Google Scholar]
  24. Talwar C, Nagar S, Kumar R, Scaria J, Lal R et al. Defining the environmental adaptations of genus Devosia: insights into its expansive short peptide transport system and positively selected genes. Sci Rep 2020; 10:1151 [View Article] [PubMed]
     [Google Scholar]
  25. Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006; 22:1658–1659 [View Article] [PubMed]
     [Google Scholar]
  26. Ammari MG, Gresham CR, McCarthy FM, Nanduri B. HPIDB 2.0: a curated database for host-pathogen interactions. Database 2016; 2016:baw103 [View Article] [PubMed]
     [Google Scholar]
  27. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990; 215:403–410 [View Article] [PubMed]
     [Google Scholar]
  28. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13:2498–2504 [View Article] [PubMed]
     [Google Scholar]
  29. Assenov Y, Ramírez F, Schelhorn S-E, Lengauer T, Albrecht M. Computing topological parameters of biological networks. Bioinformatics 2008; 24:282–284 [View Article] [PubMed]
     [Google Scholar]
  30. Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJE. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 2015; 10:845–858 [View Article] [PubMed]
     [Google Scholar]
  31. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 2018; 46:W296–W303 [View Article] [PubMed]
     [Google Scholar]
  32. Ramachandran S, Kota P, Ding F, Dokholyan NV. Automated minimization of steric clashes in protein structures. Proteins 2011; 79:261–270 [View Article] [PubMed]
     [Google Scholar]
  33. Buß O, Rudat J, Ochsenreither K. FoldX as protein engineering tool: better than random based approaches?. Comput Struct Biotechnol J 2018; 16:25–33 [View Article] [PubMed]
     [Google Scholar]
  34. Kugelman JR, Johnston SC, Mulembakani PM, Kisalu N, Lee MS et al. Genomic variability of monkeypox virus among humans, Democratic Republic of the Congo. Emerg Infect Dis 2014; 20:232–239 [View Article] [PubMed]
     [Google Scholar]
  35. Ligon BL. Monkeypox: a review of the history and emergence in the Western hemisphere. Semin Pediatr Infect Dis 2004; 15:280–287 [View Article] [PubMed]
     [Google Scholar]
  36. Verma H, Kumar R, Oldach P, Sangwan N, Khurana JP et al. Comparative genomic analysis of nine Sphingobium strains: insights into their evolution and hexachlorocyclohexane (HCH) degradation pathways. BMC Genomics 2014; 15:1014 [View Article] [PubMed]
     [Google Scholar]
  37. Swetha RG, Basu S, Ramaiah S, Anbarasu A. Multi-Epitope Vaccine for Monkeypox Using Pan-Genome and Reverse Vaccinology Approaches. Viruses 2022; 14:2504 [View Article] [PubMed]
     [Google Scholar]
  38. Postigo A, Cross JR, Downward J, Way M. Interaction of F1L with the BH3 domain of Bak is responsible for inhibiting vaccinia-induced apoptosis. Cell Death Differ 2006; 13:1651–1662 [View Article] [PubMed]
     [Google Scholar]
  39. Gerlic M, Faustin B, Postigo A, Yu E-W, Proell M et al. Vaccinia virus F1L protein promotes virulence by inhibiting inflammasome activation. Proc Natl Acad Sci 2013; 110:7808–7813 [View Article] [PubMed]
     [Google Scholar]
  40. Weaver JR, Isaacs SN. Monkeypox virus and insights into its immunomodulatory proteins. Immunol Rev 2008; 225:96–113 [View Article] [PubMed]
     [Google Scholar]
  41. White SD, Jacobs BL. The amino terminus of the vaccinia virus E3 protein is necessary to inhibit the interferon response. J Virol 2012; 86:5895–5904 [View Article] [PubMed]
     [Google Scholar]
  42. Arndt WD, Cotsmire S, Trainor K, Harrington H, Hauns K et al. Evasion of the innate immune type I interferon system by monkeypox virus. J Virol 2015; 89:10489–10499 [View Article] [PubMed]
     [Google Scholar]
  43. Stricker RLO, Behrens S-E, Mundt E. Nuclear factor NF45 interacts with viral proteins of infectious bursal disease virus and inhibits viral replication. J Virol 2010; 84:10592–10605 [View Article] [PubMed]
     [Google Scholar]
  44. Hammarlund E, Dasgupta A, Pinilla C, Norori P, Früh K et al. Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by suppressing cognate T cell activation. Proc Natl Acad Sci 2008; 105:14567–14572 [View Article] [PubMed]
     [Google Scholar]
  45. Benfield CTO, Ren H, Lucas SJ, Bahsoun B, Smith GL. Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection. J Gen Virol 2013; 94:1647–1657 [View Article] [PubMed]
     [Google Scholar]
  46. Torres AA, Macilwee SL, Rashid A, Cox SE, Albarnaz JD et al. The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling. PLoS Pathog 2022; 18:e1010277 [View Article] [PubMed]
     [Google Scholar]
  47. Schröder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J 2008; 27:2147–2157 [View Article] [PubMed]
     [Google Scholar]
  48. Pichlmair A, Kandasamy K, Alvisi G, Mulhern O, Sacco R et al. Viral immune modulators perturb the human molecular network by common and unique strategies. Nature 2012; 487:486–490 [View Article] [PubMed]
     [Google Scholar]
  49. Zhou W, He Y, Rehman AU, Kong Y, Hong S et al. Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection. Nat Neurosci 2019; 22:205–217 [View Article] [PubMed]
     [Google Scholar]
  50. Gileva IP, Nepomnyashchikh TS, Antonets DV, Lebedev LR, Kochneva GV et al. Properties of the recombinant TNF-binding proteins from variola, monkeypox, and cowpox viruses are different. Biochim Biophys Acta 2006; 1764:1710–1718 [View Article] [PubMed]
     [Google Scholar]
  51. Alejo A, Ruiz-Argüello MB, Ho Y, Smith VP, Saraiva M et al. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus. Proc Natl Acad Sci 2006; 103:5995–6000 [View Article] [PubMed]
     [Google Scholar]
  52. Antonets DV, Nepomnyashchikh TS, Shchelkunov SN. SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family. BMC Res Notes 2010; 3:271 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000987
Loading
Monkeypox virus: phylogenomics, host–pathogen interactome and mutational cascade
M Gen 9, 000987 (2023); https://doi.org/10.1099/mgen.0.000987
/content/journal/mgen/10.1099/mgen.0.000987
/content/journal/mgen/10.1099/mgen.0.000987
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error