Virulence differences of mpox (monkeypox) virus clades I, IIa, and IIb.1 in a small animal model

Human mpox (monkeypox), a disease with similarities to smallpox, is endemic in Africa where it has persisted as a zoonosis with limited human-to-human spread. Unexpectedly, the disease expanded globally in 2022 driven by human-to-human transmission outside of Africa. It is not yet known whether the latter is due solely to behavioral and environ-mental factors or whether the mpox virus is adapting to a new host. Genome sequencing has revealed differences between the current outbreak strains, classified as clade IIb, and the prior clade IIa and clade I viruses, but whether these differences contribute to virulence or transmission has not been determined. We demonstrate that the wild -de-rived inbred castaneous mouse provides an exceptional animal model for investigating clade differences in mpox virus virulence and show that the order is clade I > clade IIa > clade IIb.1. The greatly reduced replication of the clade IIb.1 major outbreak strain in mice and absence of lethality at 100 times the lethal dose of a closely related clade IIa virus, despite similar multiplication in cell culture, suggest that clade IIb is evolving diminished virulence or adapting to other species.

Automated summary

Monkeypox, a disease similar to smallpox, has become endemic in Africa with limited human-to-human transmission. However, in 2022, the disease spread globally, driven by human-to-human transmission outside of Africa. It is still unclear whether this is due to behavioral factors or the virus adapting to a new host. Genome sequencing revealed differences between the current outbreak strain (clade IIb) and previous strains (clade IIa and clade I), but the impact of these differences on virulence or transmission is yet to be determined. Using a mouse model, researchers found that the clade I virus was more virulent than the clade IIa and IIb.1 strains, suggesting that clade IIb may be evolving diminished virulence or adapting to other species.