Patterns of genomic deletions in monkeypox virus during the 2022 outbreak in the United States

Crystal M. Gigante (), Daisy McGrath, Sophia Sukkestad, Hui Zhao, Mengfei Peng, Jade Takakuwa, Kimberly Wilkins, Vaughn Wicker, Audrey Matheny, Theodora Khan, Whitni B. Davidson, Mili Sheth, Alex Burgin, Julie Hand, Gillian Richardson, Danielle Haydel, Mark Burroughs, Jasmine Padilla, Justin S. Lee, Dhwani Batra, Ethan E. Hetrick, Dakota T. Howard, Kyle O’Connell, Jessica L. Rowell, Shatavia Morrison, Sarah Gillani, Michelle Lee, Anil Mangla, David Blythe, Robert Myers, Lynsey Kovar, Matthew H. Seabolt, Michael R. Weigand, Panayampalli S. Satheshkumar, Andrea M. McCollum, Christina L. Hutson and Yu Li
Additional contact information
Crystal M. Gigante: Centers for Disease Control and Prevention
Daisy McGrath: Centers for Disease Control and Prevention
Sophia Sukkestad: Centers for Disease Control and Prevention
Hui Zhao: Centers for Disease Control and Prevention
Mengfei Peng: Centers for Disease Control and Prevention
Jade Takakuwa: Centers for Disease Control and Prevention
Kimberly Wilkins: Centers for Disease Control and Prevention
Vaughn Wicker: Centers for Disease Control and Prevention
Audrey Matheny: Centers for Disease Control and Prevention
Theodora Khan: Centers for Disease Control and Prevention
Whitni B. Davidson: Centers for Disease Control and Prevention
Mili Sheth: Centers for Disease Control and Prevention
Alex Burgin: Centers for Disease Control and Prevention
Julie Hand: Louisiana Department of Health
Gillian Richardson: Louisiana Department of Health
Danielle Haydel: Louisiana Department of Health
Mark Burroughs: Centers for Disease Control and Prevention
Jasmine Padilla: Centers for Disease Control and Prevention
Justin S. Lee: Centers for Disease Control and Prevention
Dhwani Batra: Centers for Disease Control and Prevention
Ethan E. Hetrick: Centers for Disease Control and Prevention
Dakota T. Howard: Centers for Disease Control and Prevention
Kyle O’Connell: Centers for Disease Control and Prevention
Jessica L. Rowell: Centers for Disease Control and Prevention
Shatavia Morrison: Centers for Disease Control and Prevention
Sarah Gillani: DC Health
Michelle Lee: DC Health
Anil Mangla: DC Health
David Blythe: Maryland Department of Health
Robert Myers: Maryland Department of Health
Lynsey Kovar: Centers for Disease Control and Prevention
Matthew H. Seabolt: Centers for Disease Control and Prevention
Michael R. Weigand: Centers for Disease Control & Prevention
Panayampalli S. Satheshkumar: Centers for Disease Control and Prevention
Andrea M. McCollum: Centers for Disease Control and Prevention
Christina L. Hutson: Centers for Disease Control and Prevention
Yu Li: Centers for Disease Control and Prevention

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Poxviruses have a low overall rate of point mutations but are known to exhibit genomic duplications and deletions that can influence viral evolution. We examine the prevalence of large deletions in clade IIb monkeypox virus (MPXV) genomes during the global 2022 outbreak. We observe thirty-one distinct deletions, ranging from 573 to 21,576 bp among over 2000 MPXV genomes during 2022 − 2023 in the United States (U.S.). Almost all deletions are present in the first 25,000 bp or last 50,000 bp of the MPXV genome, excluding the terminal 500 bp. The large deletions result in extensive predicted gene loss as well as novel predicted gene products. Most unique deletions are observed in one case; however, one 3370 bp deletion mutant predominated in a U.S. state during late 2022 and a different 913 bp deletion may have arisen independently multiple times across several MPXV sub-lineages and multiple countries. The recurrent presence of large deletion mutants provides evidence of a mechanism of poxvirus evolution by genomic deletion and gene loss. While no deletion emerged in a dominant variant during 2022 − 2023, large deletions have the potential to result in viruses in which a therapeutic or diagnostic target is deleted.

Date: 2025
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DOI: 10.1038/s41467-025-64003-y

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