The strain of Mpox behind the 2022 outbreak was a weakened form of the virus, which may have helped to spread it faster, a new study from the University of Surrey reports. The findings show that the virus acquired mutations before it spread globally. These mutations, which are absent in current circulating forms of the virus in parts of Africa, cause less severe symptoms in patients, who unknowingly may have spread the virus across borders.

Mpox is a viral infection which causes flu-like symptoms and leads to the development of a blistering rash. The virus is a member of the orthopoxvirus family, which also includes smallpox, which was eliminated more than 40 years ago due to vaccination programmes. Such is the growing concern regarding Mpox, the World Health Organisation has twice issued a Public Health Emergency of International Concern (PHEIC), the highest alert level for an extraordinary global health event.

Professor Maluquer de Motes, Professor of Virology at the University of Surrey, said:

“Outbreaks of Mpox across the globe are becoming more common and continue to cause concern amongst populations in regions affected. The virus has established human-to-human transmission chains and the dangers it poses cannot be underestimated.

“Although a vaccine is now in existence, supply chain issues remain and it is often a logistical challenge to ensure those who are most at risk are vaccinated. The best form of defence is to arm ourselves with as much knowledge about the virus and how it is evolving.”

During the study, led by Professor Maluquer de Motes, scientists analysed the Mpox strain (Clade IIB, lineage B.1) which infected over 100,000 people in 120 countries in 2022 and compared it to an ancestral form of the virus (Clade IIB lineage A.1) from which it derived.

Scientists found that the genetic variation between the viruses was minimal, with only 46 nucleotides differing between the two out of a possible 197,000 nucleotides, resulting in the 2022 strain being less severe than lineage A.1. This strain was found to have a reduced ability to disseminate between cells and had the ability to evade the body’s immune response. Further analysis found that the 2022 strain induced higher levels of the protein IFNB, a protein that acts as the body’s frontline defence against viruses and showed a reduced ability to suppress signals from proteins responsible for decreasing inflammation.

Examining the impact of the virus on murine models, scientists found that the 2022 strain was less aggressive to the overall health of the mice who limited virus dissemination more effectively and had an increased survival rate after exposure to this strain compared to lineage A.1.

Scientists found that the mutations were not caused by virus replication errors, but by enzymes in the human body, known as APOBEC3. As the virus circulated in humans, the enzymes introduced mutations that weakened the virus. Scientists theorise that these mutations might have helped the virus spread globally, as a weakened form of the virus enabled patients to continue with everyday life, interact with others and unknowingly spread the virus.

Professor Maluquer de Motes, added:

“We were very fortunate that the 2022 outbreak of Mpox contained the mutated strain of the virus, which we have found is less severe than its ancestors. The quick spread of the virus across borders and amongst people exposes the dangers of Mpox and how we are not yet fully equipped to deal with another outbreak of a viral infection.

“Compared to other viruses, the genetic composition of Mpox is huge. Typically having a difference of 46-nucleotides would not warrant such a change in the behaviour of a virus however this is not the case with Mpox. This shows us the complexity of this virus and that worldwide vigilance must remain.”

This study was published in Nature Communications.