The cause of 2022's mpox outbreak revealed

A research team led by the University of Surrey has discovered that the strain of mpox behind the 2022 outbreak was a weakened form of the virus, which may have helped it to spread faster. Their findings have been published in the journal Nature Communications.

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 the now-eliminated smallpox. The World Health Organization has twice declared mpox a Public Health Emergency of International Concern (PHEIC) — the highest alert level for an extraordinary global health event.

“Outbreaks of mpox across the globe are becoming more common and continue to cause concern amongst populations in regions affected,” said Professor Maluquer de Motes, who led the new study. “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.”

The study saw scientists analyse the mpox strain (Clade IIB, lineage B.1) which infected over 100,000 people in 120 countries in 2022 and compare it to an ancestral form of the virus (Clade IIB, lineage A.1) from which it derived. The 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. This small differentiation ultimately resulted in the 2022 strain being less severe than lineage A.1, with a reduced ability to disseminate between cells.

“Compared to other viruses, the genetic composition of mpox is huge,” de Motes said. “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.”

The scientists found that these variations 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. For example, the 2022 strain induced higher levels of the protein IFNβ, a protein that acts as the body’s frontline defence against viruses. It also showed a reduced ability to suppress signals from proteins responsible for decreasing inflammation.

The scientists found that the 2022 strain was less aggressive to the overall health of laboratory mice, who limited virus dissemination more effectively and had an increased survival rate after exposure to this strain compared to lineage A.1. The scientists thus theorise that the mutations may have helped the virus spread globally, as a weakened form of the virus would have enabled patients to continue with everyday life, interact with others and unknowingly spread the virus.

“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,” de Motes said. These mutations are however absent in current circulating forms of the virus in parts of Africa.

“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.”

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