Monkeypox: What is known about the virus mutation

The monkeypox virus that spreads across the United States and Europe is mutating surprisingly quickly, according to a study by Portuguese researchers and published in the journal Nature Medicine. It offers the most in-depth look at the genetic makeup of the virus yet.

Scientists sequence virus genomes because it is the pathogens’ “handbook” — that is, its genetic material gives us information about what the virus is, what it does and how it is likely to spread.

Virus has mutated 50 times since 2018

For the study, researchers collected samples from 15 patients with the disease and compared the genomes of the virus that infected them. Each of the patients was found to have a strain of monkeypox that can be traced back to a previous outbreak of the virus, in 2018-2019 in the UK, Israel and Singapore, and which originated in Nigeria.

More than that, though, tests showed that the virus had mutated 50 times — up to 12 times more than expected — since the previous outbreak in 2018.

“These data completely challenge what is known about the mutation rate of monkeypox,” said study author João Paulo Gomes, a researcher at Portugal’s National Institute of Health.

West African variant has low death rate

Some data on the virus was already available, but the new genome sequencing has helped researchers better understand the current outbreak. First, that the strain is mutating at an unusually rapid rate. Second, the outbreak likely started with a single case, infecting other targets in a major superspreading event.

The strain is part of the West African monkeypox clade, which is commonly reported from western Cameroon and Sierra Leone, and has a mortality rate of less than 1%. Clade, or branch, is defined as a group of organisms that can be traced back to common ancestors or a common genetic lineage.

There is another common clade of monkeypox, known as “Central African”, which is most present in the Congo basin and has mortality rates of up to 10%.

Incubation period makes tracking difficult

The incubation period, which ranges from five to 21 days, makes it difficult to track the movement of the virus. The World Health Organization identified the “index case” — the first confirmed case — as an individual who traveled from Nigeria to the United States in early May.

But researchers in Portugal dispute this idea because there would be confirmed cases in Portugal and the UK at the end of April.

If the researchers in Portugal are correct, less is known than previously thought about the current outbreak, including how it evolved and what it is likely to do next.

Where did the outbreak start?

The study authors consider it very likely that the virus was imported from a country where monkeypox is endemic, such as Nigeria, but do not rule out other possibilities.

They also believe it is possible, for example, that it has spread unnoticed among humans and/or other animals in non-endemic countries such as the UK or Singapore after the 2018-2019 outbreak.

Also, it is unclear whether the mutated version is worse than the original version. “The authors describe an unexpectedly high number of virus mutations, but their implications for the severity or transmissibility of the disease are unclear,” said Hugh Adler, a researcher at the Liverpool School of Tropical Medicine, in response to the article.

“We have not identified any change in clinical disease severity in patients diagnosed in the current outbreak,” said Adler, who has worked with smallpox patients in the UK during previous outbreaks. He did not participate in the research.

Research is still in its infancy

The cause of monkeypox is a double-stranded DNA zoonotic virus. DNA viruses mutate slower than RNA viruses like the one that causes Covid-19.

But in general there is not much knowledge about monkeypox. Researchers in Portugal, for example, cite just one other study on the genetics of the virus.

According to Adler, the study of the genetics of the virus “is still in its infancy”: “We have the genome sequence, so we have an idea of ​​what the genes are. But in terms of really understanding what they do and the implications for evolution, if genes change, there is very little research on it, compared to many other large viruses that we know of.”

The tropical medicine researcher hails Portugal’s research for providing “fascinating” new facts about the biology of smallpox, but suggests the study only took place due to the current spread of the virus in high-income countries.

“As always, if the global community had applied these same scientific resources to the monkeypox outbreaks in Africa, we might already have a stronger knowledge base.”

The disease was first discovered in a monkey in 1958, and the first human case was in 1970, in a child in the Democratic Republic of Congo.