Researchers studying the genetic make-up of the monkeypox virus have said the virus appears to have mutated widely, far more than would normally be expected.
The work was detailed in a new study published in the journal naturopathy. As part of the study, Portuguese researchers collected a total of 15 sequences of monkeypox viruses – mainly from Portugal – and reconstructed their genetic data.
Monkeypox is a rare disease believed to have animal origins. It belongs to the same family of viruses as smallpox. Usually, monkeypox is localized in west and central African countries, but this year saw the first outbreak in multiple countries, including cases with no known links to west or central Africa, with more than 3,500 cases reported Thursday, according to the US Centers for Disease Control and Prevention (CDC).
The virus can be transmitted between people through close contact with lesions, body fluids, respiratory droplets – such as direct contact – and contaminated materials. The current outbreak has created uncertainty about exactly how the virus is spreading, with far more transmissions than normal.
In the latest study, the researchers discovered around 50 genetic variations in the viruses they studied compared to those from 2018 and 2019. This is “far more than would be expected given previous estimates” of the mutation rate of orthopoxviruses, including monkeypox one type – between six and twelve times more.
These significant genetic variations could indicate “accelerated evolution”.
“Our data reveal additional clues to ongoing viral evolution and possible human adaptation,” the team wrote, adding that they had identified proteins known to interact with humans’ immune systems. However, more studies are needed to find out more about the potential role these could play in adapting the monkeypox virus to human spread.
João Paulo Gomes, head of the Genomics & Bioinformatics Unit at the National Institutes of Health in Portugal, who co-authored the study, said it’s not known if the mutations contributed to increased transmissibility between people.
“We don’t know,” he said news week. “All we know is that those extra 50 mutations were quite unexpected.
“Considering that this 2022 monkeypox virus is likely a descendant of the virus in the 2017 Nigeria outbreak, one would not expect more than five to ten additional mutations instead of the 50 or so mutations observed. We hope that specialized groups will now conduct laboratory experiments to understand whether this 2022 virus has increased its transmissibility.”
Another notable finding of the study is that most mutations are of a specific type that may have been introduced by a human defense mechanism called APOBEC3, which works by introducing mutations into viruses to prevent them from functioning properly, said Pam Vallely. Professor of Medical Virology at the University of Manchester.
“However, in this case, the mutations do not appear to render the virus incapable of viability and may help it adapt to human-to-human transmission,” said Vallely, who was not involved in the study news week. “This is just a theory that fits the current evidence, and much more work will be needed to see if this is really happening. I don’t think we can say that the mutations made it more contagious, but maybe they made it better adapted to humans.”
The researchers say their work shows that monkeypox viral genome sequencing could be accurate enough to track the spread of the current outbreak and see how transmission might change. This, in turn, would allow policymakers to introduce measures to curb the spread of monkeypox. Vaccines are already available.
Jeremy Kamil, associate professor of microbiology and immunology at Louisiana State University Health Shreveport, said news week called the study “very impressive,” but said it’s too early to say for sure whether monkeypox is evolving rapidly until we can rule out the possibility that the virus lasted “for longer than thought — perhaps initially — circulates in humans and adapts in undervalued regions of the world, such as parts of Africa where monkeypox is endemic.”
Alex Sigal, a virologist at the Africa Health Research Institute (AHRI) and associate professor at the University of KwaZulu-Natal, who was also not involved in the study, echoed Kamil’s point.
“I think this outbreak has been under the radar for a while,” he said news week. “Certainly the decreasing immunity because the smallpox vaccine is no longer given would have helped.
“[The findings are] worrying, but we’ll see if this virus continues to spread once people become aware of the signs and it breaks out in the general population. It’s contact-dependent, and unless the spread is respiratory, it should be easier to stop.”
Virus sequencing efforts also confirmed that the viruses examined belonged to a specific type of monkeypox virus known as clade 3, confirming that they are part of the broader West African type as opposed to the Central African type.
The West African version of monkeypox, with a mortality rate typically less than one percent, is much less virulent than the Central African clade 1 version, which can cause death in more than 10 percent of cases, according to the study.
Update 6/24/22 6:13 AM ET: This article has been updated with the latest monkeypox case numbers.