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Monkeypox mutating faster than expected – Lisbon scientists

With South Africa having two reported monkeypox cases, and more than 3,500 people having contracted the virus in nearly 50 countries, scientists from Portugal believe the lineage behind the current global outbreak has far more mutations than expected.

In fact, says the team, the virus seems to have undergone “accelerated evolution” and adaptation during human-to-human transmission during the outbreak, reports News24.

Mutations refer to individual changes in the virus’ genetic code. Often, virus mutations will not bear any significant implications on its ability to spread or cause disease. However, these 50 new mutations may make the monkeypox virus more infectious, the scientists suggest in their study, published in Nature Medicine.

The massive jump in the rate of mutation “is far more than one would expect considering previous estimates of the substitution rate for Orthopoxviruses”, they wrote. “Our data reveal additional clues of ongoing viral evolution and potential human adaptation.”

Monkeypox is a rare zoonotic disease (spread between animals and people), caused by infection with the monkeypox virus, which is part of the same family of viruses as smallpox. It’s transmitted from person to person via close skin contact with open skin lesions, bodily fluids, contaminated material (like bedding or clothing), or respiratory droplets coughed into the air.

The scientists behind the study collected DNA from 15 monkeypox viral samples from 2,022 cases and compared them with those from the years 2018 and 2019 from cases in the UK, Israel and Singapore (after travelling from Nigeria). Then, they reconstructed their genetic information and found that the real mutation rate was six to 12 times higher than they expected.

Monkeypox is a species of double-stranded DNA virus. This means it is better able to correct replication errors than an RNA virus, like the coronavirus and influenza, and the current monkeypox strain, therefore, should have only accumulated a handful of mutations since it first started circulating in 2017.

“Considering the genome characteristics of this type of virus, no more than one or two mutations are likely to emerge each year,” said Dr João Paulo Gomes, of Portugal’s National Institute of Health in Lisbon.

“However, considering this 2022 (strain) is possibly a descendant of one in the 2017 Nigeria outbreak, one would expect no more than five to 10 additional mutations instead of the observed about 50 mutations.”

There are several potential reasons why the virus may have seen this unexpected mutation rate, including that it may have been spreading among animals in countries where it doesn’t usually occur, without anyone noticing, and then this year, it jumped back into humans.

So far, where available, smallpox vaccines (which are effective against monkeypox) are being deployed in a few countries to manage close contacts, according to a 17 June update by the World Health Organisation.

Importantly, experts, including those in SA, have reassured that the virus is not as highly pathogenic as COVID-19 and is, therefore, unlikely to progress to a global health emergency.

Study details

Phylogenomic characterisation and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus

Joana Isidro, Vítor Borges, Miguel Pinto, Daniel Sobral, João Dourado Santos, Alexandra Nunes, Verónica Mixão, Rita Ferreira, Daniela Santos, Silvia Duarte, Luís Vieira, Maria José Borrego, Sofia Núncio, Isabel Lopes de Carvalho, Ana Pelerito, Rita Cordeiro & João Paulo Gomes.

Published in Nature Medicine on 24 June 2022

Abstract

The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 20221-6. Here, shotgun metagenomics allowed the rapid reconstruction and phylogenomic characterization of the first MPXV outbreak genome sequences, showing that this MPXV belongs to clade 3 and that the outbreak most likely has a single origin. Although 2022 MPXV (lineage B.1) clustered with 2018-2019 cases linked to an endemic country, it segregates in a divergent phylogenetic branch, likely reflecting continuous accelerated evolution. An in-depth mutational analysis suggests the action of host APOBEC3 in viral evolution as well as signs of potential MPXV human adaptation in ongoing microevolution. Our findings also indicate that genome sequencing may provide resolution to track the spread and transmission of this presumably slow-evolving dsDNA virus.

 

Nature Medicine (preview) article – Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus (Open access)

 

News24 article – As SA records second monkeypox case, scientists warn virus is mutating faster than expected (Open access)

 

See more from MedicalBrief archives:

 

Phaala warns against prejudice as SA records two monkeypox cases

 

WHO to rename monkeypox to ‘combat racism and stigma’

 

Monkeypox possibly linked to decrease in smallpox vaccine – global experts

 

CDC expresses concern over monkeypox outbreak in UK

 

 

 

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