Monkeypox Mutating Faster Than Expected

Lucy Hicks

July 05, 2022

The monkeypox virus is evolving 6-12 times faster than would be expected, according to a new study.

The virus is thought to have a single origin, the genetic data suggests, and is a likely descendant of the strain involved in the 2017-2018 monkeypox outbreak in Nigeria. It's not clear if these mutations have aided the transmissibility of the virus among people or have any other clinical implications, João Paulo Gomes, PhD, from Portugal's National Institute of Health in Lisbon, told Medscape Medical News in an email.

Since the monkeypox outbreak began in May, nearly 7000 cases of monkeypox have been reported across 52 countries and territories. As of July 5, there were 560 cases in the United States. So far, there have been no deaths.

Orthopoxviruses — the genus to which monkeypox belongs — are large DNA viruses that usually only gain one or two mutations every year. (For comparison, SARS-CoV-2 gains around two mutations every month.) One would expect five to10 mutations in the 2022 monkeypox virus compared with the 2017 strain, Gomes said.

In the study, Gomes and colleagues analyzed 15 monkeypox DNA sequences made available by Portugal and the National Center for Biotechnology Information in Bethesda, Maryland, between May 20 and May 27, 2022. The analysis revealed that this most recent strain differed by 50 single-nucleotide polymorphisms compared with previous strains of the virus in 2017-2018.

"This is far beyond what we would expect, specifically for orthopoxvirus," Andrew Lover, PhD, an epidemiologist at the University of Massachusetts Amherst School of Public Health & Health Sciences, told Medscape Medical News. He was not involved with the research. "That suggests [the virus] is trying to figure out the best way to deal with a new host species," he added.

Rodents are thought to be the natural hosts of the monkeypox virus, he explained, and, in 2022, the infection transferred to humans. "Moving into a new species can 'turbocharge' mutations as the virus adapts to a new biological environment," he explained, though it is not clear if the new mutations Gomes's team detected help the 2022 virus spread more easily among people.

Researchers also found that the 2022 virus belonged in clade 3 of the virus, which is part of the less-lethal West-African clade. While the West-African clade has a fatality rate of less than 1%, the Central African clade has a fatality rate of over 10%.

The rapid changes in the viral genome could be driven by a family of proteins thought to play a role in antiviral immunity: apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3). These enzymes can make changes to a viral genome, Gomes explained, "but sometimes the system is not 'well regulated' and the changes in the genome are not detrimental to the virus." These APOBEC3-driven mutations have a signature pattern, he said, which was also detected in most of the 50 new mutations Gomes's team identified.

However, it is not known if these mutations have clinical implications, Lover said.

The 2022 monkeypox virus does appear to behave differently than previous strains of the virus, he noted. In the current outbreak, sexual transmission appears to be very common, which is not the case for previous outbreaks, he said. Also, while monkeypox traditionally presents with a rash that can spread to all parts of the body, there have been several instances of patients presenting with just a few "very innocuous lesions," he added.

Gomes hopes that specialized lab groups will now be able to tease out whether there is a connection between these identified mutations and changes in the behavior of the virus, including transmissibility.

While none of the findings in this analysis raises any serious concerns, the study "suggests there [are] definitely gaps in our knowledge about monkeypox," Lover said. As for the global health response, he said, "We probably should err on the side of caution. …There are clearly things that we absolutely don't understand here, in terms of how quickly mutations are popping up."

Gomes and Lover report no relevant financial relationships.

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