Patterns of genomic deletions in monkeypox virus during the 2022 outbreak in the United States
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.
Authors
- Shatavia S. Morrison (ORCID: https://orcid.org/0000-0002-4658-5951)
- Vaughn Wicker (ORCID: https://orcid.org/0000-0003-4407-9489)
- Audrey Matheny (ORCID: https://orcid.org/0000-0002-8421-8167)
- Theodora Khan
- Gillian Richardson
- Dakota Howard (ORCID: https://orcid.org/0000-0002-7674-0385)
- Sarah Gillani
- Andrea M. McCollum (ORCID: https://orcid.org/0000-0002-9136-818X)
- Kyle O’Connell
- Mark Burroughs
- Jessica Rowell
- Mengfei Peng (ORCID: https://orcid.org/0000-0002-1206-4883)
- Jasmine Padilla (ORCID: https://orcid.org/0009-0005-0812-271X)
- Kimberly Wilkins
- Lynsey Kovar
- Ethan E. Hetrick (ORCID: https://orcid.org/0000-0002-6508-5987)
- Christina L. Hutson (ORCID: https://orcid.org/0000-0001-7998-9728)
- Alex B. Burgin (ORCID: https://orcid.org/0009-0008-3880-5361)
- Panayampalli S. Satheshkumar (ORCID: https://orcid.org/0000-0003-1472-1418)
- Danielle Haydel
- Robert A. Myers (ORCID: https://orcid.org/0000-0001-5533-1198)
- Matthew H. Seabolt (ORCID: https://orcid.org/0000-0002-0336-5545)
- Michael R. Weigand (ORCID: https://orcid.org/0000-0002-7278-0160)
- Yu Li (ORCID: https://orcid.org/0000-0002-4844-3359)
- Anil T. Mangla (ORCID: https://orcid.org/0009-0001-1759-1105)
- Dhwani Batra (ORCID: https://orcid.org/0000-0002-6789-6396)
- Sophia Sukkestad (ORCID: https://orcid.org/0000-0002-0877-0400)
- Justin Lee (ORCID: https://orcid.org/0000-0002-6539-2637)
- Michelle Lee (ORCID: https://orcid.org/0000-0002-7847-4471)
- Hui Zhao (ORCID: https://orcid.org/0000-0002-3816-7733)
- Mili Sheth
- Whitni B. Davidson
- David Blythe (ORCID: https://orcid.org/0000-0002-9875-8113)
- D McGrath (ORCID: https://orcid.org/0009-0004-3603-3960)
- Jade Takakuwa
- Julie Hand
Institutions
- Leidos (United States) (US)
- Louisiana State Department of Health and Hospitals (US)
- Centers for Disease Control and Prevention (US)
- Association of Public Health Laboratories (US)
- Deloitte (United States) (US)
- Maryland Department of Health (US)
- Centers for Disease Control and Prevention (UG)
- District of Columbia Department of Health (US)
- National Center for Emerging and Zoonotic Infectious Diseases (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-08
- DOI
- https://doi.org/10.1038/s41467-025-64003-y
- Citations
- 2
- Primary Topic
- Poxvirus research and outbreaks
- Type
- article
- Field-Weighted Citation Impact
- 2.07
Funders
- U.S. Department of Energy
- Yale University
- Florida Department of Health
- District of Columbia Department of Health
- Centers for Disease Control and Prevention
- Oak Ridge Institute for Science and Education