Monkeypox virus (MPXV) belongs to the Poxviridae family and the Orthopoxvirus genus. It is an enveloped, double-stranded DNA virus. The virus was first discovered in 1958 in laboratory monkey colonies and is one of the most significant members of the Orthopoxvirus genus after the variola virus. The natural reservoir of the monkeypox virus is primarily certain rodent species in Africa, establishing transmission cycles of "animal-to-animal" and "animal-to-human." Genetically, the monkeypox virus is highly homologous to the variola virus, with a conserved core genome structure, though genetic variations exist in the terminal regions. These differences influence the virus's host range, transmission capacity, and pathogenic characteristics.

The monkeypox virion is typically brick-shaped or ovoid, with a diameter of approximately 200–250 nm, exhibiting the complex multilayered structure characteristic of poxviruses. Mature virions exist in two primary infectious forms: intracellular mature virions (IMV) and extracellular enveloped virions (EEV). IMV is the basic form of the virus, with a structure consisting of, from the inside out: a dumbbell-shaped core composed of viral genomic DNA and core proteins; a protein lateral body and core wall surrounding the core; and an outermost lipid envelope embedded with various virus-specific proteins. EEV, on the other hand, contains an additional envelope derived from the host cell's internal membrane system. The monkeypox virus genome is a linear double-stranded DNA approximately 197 kb in length, with hairpin loop structures at the termini. The genome encodes about 190 open reading frames, including various enzymes and immunomodulatory proteins involved in viral replication, transcription, and assembly. The virion surface contains several important antigenic proteins, such as A27 and L1 on the IMV surface, as well as EEV-specific proteins like B5 and A33. These proteins play key roles in viral attachment, membrane fusion, and immune recognition. The monkeypox virus replicates and assembles within independent "virus factories" in the host cell cytoplasm, a unique cytoplasmic replication mechanism that is a key biological feature of the virus.

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