Genome Analysis Reveals Unusually Rapid Mutation of Monkeypox Virus

A new study published in Nature Medicine provides the first robust genomic analysis of the monkeypox virus that is currently spreading around the world. The study traced the virus to the 2017 monkeypox outbreak in Nigeria and showed that it rapidly produced an unusually large number of mutations that may be linked to increased human-to-human transmission.

In early May, a British resident who had recently returned from a trip to Nigeria was confirmed to have monkeypox. By the end of the month, dozens more cases had been detected around the world, from Spain, Germany and France to Australia, Mexico and the United States.

The breadth of this spread is unprecedented. Although monkeypox is endemic in parts of Central and West Africa, it has never before spread widely around the world, and scientists quickly began studying the virus’ genome to understand where it came from and how it might differ from what has been seen in the past .

Led by a team of scientists in Portugal, the new study looked at 15 different virus samples from infected people. The first genomic link found in the study was related to clusters of monkeypox cases identified in Israel, Singapore and the UK in 2018 and 2019.

These cases were all previously associated with returning travellers from Nigeria, and the genomic association was further traced to the 2017/2018 monkeypox outbreak in Nigeria.

Perhaps the most unexpected finding of the new study is the revelation that the current monkeypox strain appears to have undergone an unusually rapid period of mutation. The project’s lead researcher, João Paulo Gomes, said that one would normally only expect to see the virus accumulate a few new mutations a year, but the iterations currently circulating appear to contain around 50 new mutations.

“Considering that this 2022 monkeypox virus may be a descendant of the 2017 Nigerian monkeypox virus, we would expect no more than five to 10 additional mutations (compared to the imported virus in 2018-2019), while Not the 50 or so mutations observed,” Gomes said in an opinion piece for vaccine charity Gavi.

The prevailing assumption is that between 2019 and 2022, the virus has circulated undetected in an endemic country for several years. The current global outbreak is likely to originate from a single source and then be amplified by one or more superspreader events in early 2022, leading to widespread mass transmission that was subsequently detected in April and May.

In an interview with MedPage Today, Gomes said many of the mutations detected so far are related to human immune system proteins. This suggests that the virus may have rapidly adapted to human-to-human transmission.

Gomes told MedPage Today: “The multiple mutations we see in human-to-human transmission in 2022 affect proteins involved in the human immune system, so it could mean an adaptation process in humans. And, yes Yes, it appears to be occurring faster than expected, which is also consistent with the observation that 2022 (strain) is too mutated compared to its ancestor.”

Hugh Adler, of the Liverpool School of Tropical Medicine, said the new study highlights how little we know about the genetics of monkeypox, a virus that has been circulating for more than 50 years. Adler also stressed that it’s too early to know what the new mutations cited in the study mean for transmission or disease severity.

Adler explained: “The authors describe an unexpectedly high number of mutations in the virus, but their impact on disease severity or transmissibility is unclear. We did not find clinical disease severity in patients diagnosed in the current outbreak. any changes.”

As of June 24, 2022, more than 4,100 monkeypox cases have been reported in about 50 countries. The World Health Organization (WHO) recently convened an emergency advisory group to assess the global situation.

While the panel did acknowledge the “urgent nature of the event,” it declined to recommend that WHO declare the outbreak a Public Health Emergency of International Concern (PHEIC). WHO declares a public health emergency of international concern when a new disease is identified that is spreading internationally and requires a coordinated global response to manage. There are currently two infectious diseases declared PHEIC: polio and COVID-19.

The WHO’s hesitation in declaring the monkeypox outbreak a public health emergency has been criticized by some infectious disease experts. In an interview with Science Insider, global health policy expert Alexandra Phelan questioned the purpose of the WHO’s emergency declaration policy if it was triggered so slowly when there was an apparent spread of a new infectious disease.

“This is a global alert mechanism for public health, and I’m concerned about what it means for community transmission to wait a few weeks before fully grabbing political attention,” Phelan said in an email to Science. “I think it’s very clear that it’s time to reconsider what the goals of PHEICs are and whether the standards are fit for purpose to remind the global community and fair enough in an interconnected world.”

Raina MacIntyre, an infectious disease expert who has studied monkeypox in the past, said the transmission of the new virus was “absolutely unusual”. While calling on global health authorities to do what they can to stop the spread of the virus, she speculates that COVID-19 may have played a role in this sudden outbreak.

While weakened immunity from past smallpox vaccinations may have been a factor in the increased spread of the virus, MacIntyre wondered whether SARS-CoV-2 infection compromised people’s immune responses, making them more susceptible to monkeypox infection.

“As people recover from COVID, their immune systems are compromised,” MacIntyre wrote in an article for The Conversation. “As a result, people who have had COVID may be more susceptible to other infections. We’ve seen the same with measles infections. This weakens the immune system and increases the risk of other infections for the next two to three years.”

The new study was published in Nature Medicine.