As researchers at the Minnesota Department of Health in St. Paul were sequencing samples of the monkeypox virus a few months ago, they made a surprising discovery. In one sample collected from an infected person, a large chunk of the virus’s genome was missing, and another chunk had moved to an entirely different spot in the sequence.
Crystal Gigante, a microbiologist at the US Centers for Disease Control and Prevention in Atlanta, Georgia, was called in to help examine the mutations. She and her colleagues found similar deletions and rearrangements in a handful of other monkeypox genomes collected in the United States, according to a report that they posted on 17 September on the preprint server bioRxiv that has not undergone peer review
Although scientists aren’t alarmed, they are monitoring the situation carefully to understand why the alterations have appeared, and what they might mean for the global monkeypox outbreak. These mutations are a stark reminder that even poxviruses — which are DNA viruses that tend to evolve more slowly than RNA viruses, such as the SARS-CoV-2 coronavirus — will change over time, says Elliot Lefkowitz, a computational virologist at the University of Alabama at Birmingham. And the more the monkeypox virus is transmitted between humans, he adds, the more opportunities it will have to evolve.
The mutations assessed by Gigante weren’t the single-letter alterations that scientists are used to seeing in the SARS-CoV-2 genome. In some cases, entire genes had vanished: a stretch of about 7% of the genome was missing in a sample from an infected person in Florida. But it’s too early to tell whether the mutations are beneficial, neutral or harmful to the virus, Lefkowitz says. If health officials detect an uptick in the number of virus samples carrying these mutations, that could be a possible signal that they are helping the virus to spread.
Although scientists aren’t alarmed, they are monitoring the situation carefully to understand why the alterations have appeared, and what they might mean for the global monkeypox outbreak. These mutations are a stark reminder that even poxviruses — which are DNA viruses that tend to evolve more slowly than RNA viruses, such as the SARS-CoV-2 coronavirus — will change over time, says Elliot Lefkowitz, a computational virologist at the University of Alabama at Birmingham. And the more the monkeypox virus is transmitted between humans, he adds, the more opportunities it will have to evolve.
The mutations assessed by Gigante weren’t the single-letter alterations that scientists are used to seeing in the SARS-CoV-2 genome. In some cases, entire genes had vanished: a stretch of about 7% of the genome was missing in a sample from an infected person in Florida. But it’s too early to tell whether the mutations are beneficial, neutral or harmful to the virus, Lefkowitz says. If health officials detect an uptick in the number of virus samples carrying these mutations, that could be a possible signal that they are helping the virus to spread.Orthopoxviruses, a genus of poxviruses that includes the monkeypox virus and the variola virus, which causes smallpox, share a core set of about 174 genes at the centre of their genomes. But their terminal regions are more variable and contain fewer essential genes. Some of the genes in these regions are thought to encode proteins that help to disarm hosts’ immune responses, and are tailored for infecting specific hosts, Lefkowitz says. This underlies one hypothesis for why variola became adept at infecting humans: over the span of thousands of years, an earlier version of the virus might have lost genes from its termini that had enabled it to infect a broad range of animal species, and it eventually became a specialist at infecting humans.
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