The monkeypox virus (particles shown in this coloured image from a transmission electron microscope) is a DNA virus that readily detects and repairs small mutations in its genome, so it evolves more slowly than other pathogens.
Credit: National Institutes of Health/Science Photo Library
But the mutations discovered by the Minnesota team in the monkeypox virus appear to have escaped this repair mechanism and involve deletion of whole chunks of DNA and rearrangement of other parts. The discovery was made in the course of routine sequencing of the virus DNA from a patient with the disease, and was subsequently verified by Crystal Gigante, a microbiologist at the US Centers for Disease Control and Prevention in Atlanta, Georgia, who was called in to help with the investigation.
The good news is that the mutations so far don't involve the part of the DNA which codes for the protein which is the target of tecovirimat, an antiviral drug being tested for use against monkeypox in humans.
That the virus is mutating in this way is no surprise, because Eneida Hatcher, an evolutionary virologist at the National Center for Biotechnology Information in Bethesda, Maryland, co-authored a paper with Elliot Lefkowitz, in 2015 which showed that these mutations are common in poxviruses but the majority of them occur towards the ends of the DNA strands while a core group of about 174 core genes remain intact. These labile end genes are probably involved in supressing the victim's immune responses and mutations here mean they can infect multiple host species, then evolve to specific hosts by mutating these end genes while the core genes remain unaffected. At the moment, monkeypox is a 'generalist' that can infect several different species; the danger is that it could become a 'specialist' in humans much like smallpox did.
The team have made their paper available, open access, ahead of peer-reviewed publication on the pre-print server, bioRxiv. In the abstract, they say:
AbstractEntering the deluded fantasy land of Creationism for a moment, these mutations have to be seen as the deliberate modification of the virus by the one and only putative intelligent [sic] designer, because only that magic entity is capable of changing an organism's genome. Outside that childish fantasy of course, these mutations and their increased frequency in the viral genome are predictable results of evolution by mutation and natural selection - something that every dedicated Creationist must reject by dogma in favour of a childish notion that leaves their god looking like a celestial sadistic malevolence trying to find better ways to make its creation suffer.
Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3’ terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance.
Crystal M. Gigante, Matthew Plumb, Ali Ruprecht, et al, (2022)
Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA
bioRxiv 2022.09.16.508251; doi: https://doi.org/10.1101/2022.09.16.508251
Copyright: © 2022 The authors. Published by bioRxiv
Open access
Reprinted under a Creative Commons CC0 1.0 Universal (CC0 1.0) Public Domain Dedication license
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