Mpox outbreak in 2022 caused by less severe form of the virus, study reveals
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The strain of mpox behind the 2022 outbreak was a weakened form of the virus, which may have helped it spread faster, a new study from the University of Surrey reports. The findings, published in the journal Nature Communications, show that the virus acquired mutations before it spread globally. These mutations, which are absent from forms of the virus currently circulating in parts of Africa, cause less severe symptoms in patients, who may have unknowingly spread the virus across borders.
Mpox is a viral infection that 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, eliminated more than 40 years ago through vaccination programs. Because of growing concern about mpox, the World Health Organization has twice declared 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 among populations in affected regions. The virus has established human-to-human transmission chains, and the dangers it poses cannot be underestimated.
"Although a vaccine is now available, supply chain issues remain, and it is often a logistical challenge to ensure those most at risk are vaccinated. The best form of defense is to arm ourselves with as much knowledge about the virus and how it is evolving."
Comparing the outbreak strain
During the study, led by Professor Maluquer de Motes, scientists analyzed the mpox strain (Clade IIB, lineage B.1) that infected more than 100,000 people in 120 countries in 2022 and compared it with an ancestral form of the virus (Clade IIB lineage A.1) from which it was derived.
Scientists found that genetic variation between the viruses was minimal, with only 46 nucleotides differing between the two out of a possible 197,000 nucleotides. The 2022 strain was less severe than lineage A.1. It had a reduced ability to disseminate between cells and could evade the body's immune response.
Further analysis found that the 2022 strain induced higher levels of the protein IFNB, which acts as the body's frontline defense against viruses, and showed a reduced ability to suppress signals from proteins responsible for decreasing inflammation.
Mutations shaped by human enzymes
Examining the impact of the virus on murine models, scientists found that the 2022 strain was less harmful to the overall health of the mice, which limited virus dissemination more effectively and had a higher survival rate after exposure to this strain than 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 theorize that these mutations might have helped the virus spread globally, as a weakened form 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 among 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, a difference of 46 nucleotides would not warrant such a change in the behavior 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."
Publication details
Rebecca P. Sumner et al, APOBEC3-driven attenuation of the 2022 global outbreak monkeypox virus relative to its clade IIb ancestor, Nature Communications (2026). DOI: 10.1038/s41467-026-76580-7
Journal information: Nature Communications
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