NEW YORK – The mpox virus (MPXV) has spread via human-to-human transmission for at least seven years, according to a new genome analysis that tracked viral mutations introduced by human host APOBEC3 deaminase enzymes.
"These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control," senior and corresponding author Andrew Rambaut, an ecology and evolution researcher at the University of Edinburgh, and his colleagues wrote in Science on Thursday.
Based on mutation profiles in mpox isolates collected from infected individuals in the spring of 2022 — which contained 42 single-nucleotide changes relative to previously described mpox isolates — the researchers reasoned that mutations introduced by antiviral APOBEC3 enzymes found in human hosts may serve as a marker for person-to-person transmission.
With that in mind, the team attempted to untangle host APOBEC3 effects on the MPXV genome over time using whole-genome sequences for MPXV isolates linked to documented human infections between 2017 and 2022, along with a single outgroup sequence going back to 1971 in Nigeria.
"We assess the extent to which APOBEC3 has acted on MPXV and explore whether this is the source of the elevated mutation rate observed since 2017," the authors explained.
Indeed, their results suggested that human-to-human transmission of the virus is marked by APOBEC3-based MPXV editing, introducing new mutations that were concentrated in a fast-changing clade IIb lineage that contains an outbreak-linked sub-clade. Such changes were far less common in the clade I and clade IIa lineages, which have included zoonotic isolates from Central Africa and West Africa, respectively.
"We suggest that the APOBEC3-driven evolution of recent clade IIb MPXV is a signature of a switch to sustained transmission within the human population," the authors reported.
Along with follow-up analyses focused on the nucleotide and amino acid consequences of the human infection-linked mutations, the investigators used APOBEC3-related mutation rates to retrace the MPXV's history in humans, performing phylogenetic analyses that pointed to steady human-to-human spread since late 2015 or early 2016.
The finding contrasts with earlier mpox cases, which tended to reflect occasional zoonotic spread to humans — particularly infants and children — from infected reservoir animals such as rodents in parts of Central and West Africa where the virus is endemic, the study's authors explained.
While their results hinted that such zoonotic spread continues to occur for clade I viruses in Central Africa, the investigators cautioned that at the same time, human-to-human transmission may be occurring in parts of Africa where MPXV is considered endemic.
"Many countries lack the surveillance to detect MPXV cases, and if sustained human-to-human transmission has been ongoing since 2015 to 2016, it is plausible that there are other populations that are currently enduring epidemics," the authors wrote.
"It is critical that global public health affords MPXV cases in countries that are historically considered to have endemic reservoir species equal attention and concern to those elsewhere," they suggested. "Surveillance needs to be global if MPXV is to be eliminated from the human population and then prevented from reemerging."