Monkeypox virus emerges from the shadow of its more infamous cousin: family biology matters

Monkeypox virus (MPXV) is closely related to the infamous variola (smallpox) virus, causing a febrile rash illness in humans similar to but milder than smallpox. In the twentieth century, human monkeypox had been mostly a rare zoonotic disease confined to forested areas in West and Central Africa. However, the case number and geographic range have increased significantly in this century, coincided with the waning of the smallpox vaccine-induced immunity in the global population. The outbreak of human monkeypox in multiple countries since May 2022 has been unusual in its large case number and the absence of direct links to endemic countries, raising concerns for a possible change in monkeypox transmission pattern that could pose a greater global threat. Here, we review aspects of MPXV biology that are relevant for risk assessment and preparedness for a monkeypox epidemic, with an emphasis on recent progress in understanding of the virus host range, evolutionary potential, and neutralization targets.