Genomic insights into the changing landscape of MPXV outbreaks
Historically, mpox was regarded as a zoonotic disease with limited capacity for onward transmission. In 2022, the global sweep of MPXV revealed that the virus could persist in the human population. The virus genomes revealed an excess of TC->TT and GA->AA mutations, caused by editing of a host anti-viral enzyme APOBEC3. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that estimated that MPXV had been circulating in humans since at least 2016. Since 2023 unusually high numbers of mpox cases have been reported in the Democratic Republic of Congo. Both genomic analysis and epidemiological investigation have revealed the dual role of zoonotic spillover and sustained human-transmission in these recent outbreaks and highlight the need for adaptable public health messaging around MPXV as well as outbreak management and control.
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