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APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since 2016

This Club EvMed event occurred on March 5, 2024. Learn more about Club EvMed at

This conversation was led by Dr. Áine O’Toole.

Historically, mpox has been characterized as a zoonotic disease, primarily transmitted through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were identified spreading internationally beyond regions with established endemic reservoirs. Upon sequencing the first cases from 2022, it was found that they exhibited 42 nucleotide differences from the closest previously sampled mpox virus (MPXV). Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function.

Assuming that APOBEC3 editing is a hallmark of human MPXV infection, we developed a dual-process phylogenetic molecular clock. This clock, estimating a rate of approximately six APOBEC3 mutations per year, suggests that MPXV has been circulating in humans since at least 2016. These findings, demonstrating sustained transmission of MPXV, represent a significant departure from the traditional understanding of MPXV epidemiology as a zoonosis. They underscore the importance of re-evaluating public health communication related to MPXV and adjusting strategies for outbreak management and control.


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