Monkeypox is an infectious disease caused by the monkeypox virus (MPXV), a double-stranded DNA virus, that belongs to the Orthopoxvirus genus of the Poxviridae family. The virus was first discovered in 1958 as the cause of outbreaks of a pox-like disease in monkeys kept for research in Denmark. Human disease was first identified in 1970 in a 9-month-old boy in the Democratic Republic of the Congo. Orthopoxviruses can cause disease in humans and other mammals. Symptomatic infection typically results in the formation of lesions, skin nodules or disseminated rash. Other orthopoxviruses (OPXVs) pathogenic to humans include Cowpox virus and Variola virus (causing smallpox). Smallpox vaccines derived from Vaccinia virus, also an orthopoxvirus, were a key tool for the eradication of smallpox, which was achieved in 1980.

MPXV was named based on its initial detection in captive monkeys and, although the virus continues to affect species of monkeys in Africa, the main animal reservoirs are likely small forest mammals such as rodents and squirrels. There are two known clades of MPXV: clade I, mainly found in the Congo Basin region, and clade II, which contains two subclades, designated as clade IIa and clade IIb. (6) Clade IIb is the predominant strain in the ongoing global outbreak, which was recognized in May 2022 and has disproportionally affected men who have sex with men. Over many years and especially since 2012, an increasing trend in clade I detections has also been reported in the Democratic Republic of the Congo with a marked rise in cases reported since 2023.

MPXV has a linear DNA genome and is approximately 200 kb long. The genome has a highly conserved central region coding for replication and its assembly machinery. (10)In addition, the genome has the more variable ends that contain inverted terminal repeats (ITRs) ends, which contain genes involved in host range determination and pathogenesis. MPXV contains at least 4 open reading frames (ORFs) in the ITR region (11). For clade I and clade II, deletions and duplications of parts of the less conserved regions in the MPXV genome termini have been described (11–17). These deletions can lead to loss of detection with MPXV clade specific NAAT tests.