Nature The human interaction with mpox has changed across its entire endemic range, revealing the endemic and pandemic risk of monkeypox virus and the current knowledge gaps on its biology that hamper virus control.
Humans are an ecological niche for orthopoxviruses (OPXV) such as mpox, a niche originally filled by smallpox (variola virus; VARV). Since VARV was eradicated by vaccination with vaccinia virus (VACV)1, the human niche for OPXV has been vacant, with sporadic OPXV zoonoses from mpox (MPXV) (in Africa), cowpox virus (North Europe), Abatino poxvirus (South Europe), Akhmeta virus (West Asia) and Alaskapox virus (North America) (reviewed in ref. 2). There are also numerous VACV zoonoses in South America attributed to VACV established in rodent populations during the smallpox eradi- cation campaign. The common feature of OPXV zoonoses is the absence of human-to-human (H2H) transmission, except for MPXV, which made limited H2H chains that would generally end after two or three transmissions3.