Inverted repeats in the monkeypox virus genome are hot spots for mutation

Dobrovolná, Michaela, Brázda, Václav, Warner, Emily F. and Bidula, Stefan ORCID: https://orcid.org/0000-0002-3790-7138 (2022) Inverted repeats in the monkeypox virus genome are hot spots for mutation. Journal of Medical Virology, 95 (1). ISSN 0146-6615

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Abstract

The current monkeypox virus (MPXV) strain differs from the strain arising in 2018 by 50+ single nucleotide polymorphisms (SNPs) and is mutating much faster than expected. The cytidine deaminase apolipoprotein B messenger RNA editing enzyme, catalytic subunit B (APOBEC3) was hypothesized to be driving this increased mutation. APOBEC has recently been identified to preferentially mutate cruciform DNA secondary structures formed by inverted repeats (IRs). IRs were recently identified as hot spots for mutation in severe acute respiratory syndrome coronavirus 2, and we aimed to identify whether IRs were also hot spots for mutation within MPXV genomes. We found that MPXV genomes were replete with IR sequences. Of the 50+ SNPs identified in the 2022 outbreak strain, 63.9% of these were found to have arisen within IR regions in the 2018 reference strain (MT903344.1). Notably, IR sequences found in the 2018 reference strain were significantly lost over time, with an average of 32.5% of these sequences being conserved in the 2022 MPXV genomes. This evidence was highly indicative that mutations were arising within IRs. This data provides further support to the hypothesis that APOBEC may be driving MPXV mutation and highlights the necessity for greater surveillance of IRs of MPXV genomes to detect new mutations.

Item Type:	Article
Additional Information:	Funding Information: No funding was received for this manuscript.
Uncontrolled Keywords:	apobec,evolution,inverted repeats,monkeypox,mutation,virology,infectious diseases,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2406
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Pathogen Biology Group
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	15 Dec 2022 04:08
Last Modified:	01 Oct 2024 01:55
URI:	https://ueaeprints.uea.ac.uk/id/eprint/90159
DOI:	10.1002/jmv.28322

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